TCS0038

Written evidence submitted by Richard Lea and Gary England,

School of Veterinary Medicine, University of Nottingham

Executive summary

Key findings:

Chemical contaminants at concentrations commonly found in the household are capable of altering fertility in the adult.

Children may be particularly at risk of household exposure to chemicals.

Recommendation:

That the committee support a review of current safety limits of the relevant chemicals.

• Our primary research focus is on the effects of chemical pollutants on human and dog male fertility. The domestic dog shares our homes and environment, is exposed to the same household chemicals and suffers from the same exposure related adverse effects as the human. Consequently, the dog provides a means of assessing adverse chemical effects on the human
• This is evidenced by:
• A decline in canine sperm quality over time (26 years) that parallels the many reports of a similar decline in the human (Lea et al., 2016)
• The detection of flame retardants (poly-brominated diethyl ethers: PBDEs), industrial chemicals (polychlorinated biphenyls: PCBs) and plastic derived di-ethylhexyl phthalate (DEHP) in sperm samples, collected from dogs as part of routine reproductive examination, and in discard tissue (testis) obtained from routine neuterings. Concentrations of these pollutants in samples match those reported in the human.
• Demonstration of adverse effects of PCB153 and DEHP on sperm motility and DNA integrity when tested at environmental/ household concentrations. This was demonstrated with both dog and human sperm samples (Sumner et al., 2019).
• Since the concentrations of the chemicals tested are low and below the reported No-Observed-Adverse-Effect-Level (NOAEL) values for each chemical independently, the safety limits of these chemicals require review.
• PBDE’s, PCB’s and DEHP are also detectable in commercially available pet foods suggesting that diet may be one source of exposure.

Introduction

1.               Richard Lea (Reader & Associate Professor in Reproductive Biology) and Gary England (Dean & Professor of Comparative Veterinary Medicine) are based in the School of Veterinary Medicine, University of Nottingham. Dr Lea leads a research programme on the effects of environmental chemicals on mammalian fertility and reproductive health. His work is based on the concept that the domestic dog in our homes is exposed to the same household chemical toxins as the owners. Consequently, human ailments/ill health linked to exposure are likely to be replicated in the dog. Prof. England is a clinical specialist in canine reproduction, has developed several research programmes around a population of local assistance dogs and collaborates with Dr Lea.

Research Findings

2.               We have generated data showing low concentrations of PBDEs, PCBs and DEHP in sperm and that biologically relevant concentrations of two chemicals (PCB153, DEHP) are able to reduce sperm motility and the integrity of DNA in the sperm head.

3.               These data show that chemicals at concentrations markedly below other reported NOAELs, particularly PCB153, have adverse effects on reproductive health in both man and dog. Previously determined safety limits/NOAELs have been largely based on observations of rodents exposed experimentally to chemical toxins. Many of the observations tend to be visible changes in the offspring such as the lack of descent of the testicles into the scrotum. Our data show that lower concentrations of the chemicals affect the sperm with potential long term consequences for fertility and reproductive function (European Chemicals Agency support doc. on bis(2-ethylhexyl) phthalate (DEHP), 2014).

4.               Our work is focussed on direct short term effects of house chemical contaminants on sperm function and integrity (viability). The chemicals we have detected in dog sperm and/or testis are as follows:

• PCB congeners (28, 52, 101, 118, 138, 153, 180)
• PBDE congeners (28, 47, 99, 100, 153, 183)
• DEHP

5.               The detection of a majority of the above chemicals in dog semen, testis and commercially available pet food suggests that these pollutants originate in the home and/or through the diet and that they may adversely affect reproductive function. In support of this contention, we have demonstrated the following:

• Over a period of 26 years, sperm motility in a population of stud dogs has declined by 30%. These are stud dogs that live in the home environment and the decline parallels the reported decline in human sperm counts which has decreased by 50% in the last 80 years (Lea et al., 2016; Levine et al., 2017).
• Over a similar time frame, and in the same population of dogs, we have reported an increased incidence of male pups that lack testicles in the scrotum (cryptorchidism). This has also been reported in the human and to be geographically linked to the decline in sperm quality. It has therefore been postulated that this problem is also due to environmental chemical exposure (Skakkebaek et al., 2016; Lea et al., 2016).
• PCB153 and DEHP, at concentrations measured in dog semen and testis, adversely affects dog sperm function in vitro by reducing motility and increasing DNA fragmentation.
• Chemical concentrations tested were below reported NOAELs and the same two chemicals induced the same effects on human donor sperm samples (see table 1 below).
• Since increased sperm DNA fragmentation and reduced motility are reported to be an index of subfertility, these data suggest that in both species, PCBs and DEHP may be responsible for this decline.

We postulate that this constitutes evidence that chemicals, at concentrations found in the household, adversely affect sperm function and viability.

Table 1: Concentrations of PCB153 and DEHP, relative to male tract concentrations, which exhibit adverse effects on dog and human sperm. Comparable reported NOAELs are provided.

1NOAEL = No-Observed-Adverse-Effect-Level

2Sumner et al., 2019,

3European Chemicals Agency support doc. on bis(2-ethylhexyl) phthalate (DEHP), 2014

4The EFSA Journal 284, 1-137, 2005

6.               We have yet to test the effects of the other chemical contaminants present in semen on sperm function and viability. In terms of who is most at risk, our data suggest that chemical impacts on the dog are relevant to chemical impacts on adults and children in the household. Notably, children may be considered more at risk of household exposure to chemicals than adults and exposure risks from toys and childcare articles are well documented (European Chemicals Agency report on bis(2-ethylhexyl) phthalate (DEHP), 2014). With respect to our use of the dog as an indicator species for human exposure to household contaminants, we further postulate that dog exposure better approximates those of the child given the similar proximity to household sources of pollutants i.e. both are close to the ground.

7.               Methods used to measure toxic effects of chemical contaminants do not make reference to the domestic dog as a reflection of human exposure and do not include sperm co-cultures. Our data clearly show adverse effects of chemicals at concentrations previously considered safe and well below the reported safety limits. Our data on chemical contaminants on dog food at levels comparable to those found in semen and testis tissue suggest that food is a source of contamination.

8.               Although the Government 25 year plan dovetails with the Stockholm convention on eliminating PCBs and reducing persistent organic pollutants (POPs), it is important to review what constitutes a safe level of chemicals. This can be achieved by reviewing the effects of individual and mixtures of chemicals on sperm function and general fertility using the approaches described in this evidence report.

March 2019

References:

1. Sumner RN, Tomlinson M, Craigon J, England G, Lea RG. Independent and combined effects of diethylhexyl phthalate and polychlorinated biphenyl 153 on sperm quality in the human and dog. Nature Scientific Reports. 9, 3409; doi: 10.1038/s41598-019-39913-9, 2019.
2. Lea RG, Byers AS, Sumner RN, Rhind SM, Zhang Z, Freeman, SL, Moxon, R, Richardson HM, Green, M, Craigon J, England, GCW. Environmental chemicals impact dog semen quality in vitro and may be associated with a temporal decline in sperm motility and increased cryptorchidism. Nature Scientific Reports. 6, 31281; doi: 10.1038/srep31281, 2016.
3. European Chemicals Agency support document: bis(2-ethylhexyl) phthalate (DEHP), EC number: 204-211-0 adopted 11 December, 2014.
4. Levine, H, N Jorgensen, A Martino-Andrade, J Mendiola, D Weksler-Derri, I Mindlis, R Pinotti, and SH Swan 2017 Temporal trends in sperm count: a systematic review and meta-regression analysis. Human Reproduction Update 23 646-659.
5. Skakkebaek NE, Rajpert-De Meyts E, Buck Louis GM, Toppari J, Andersson AM, Eisenberg ML, Jensen TK, Jørgensen N, Swan SH, Sapra KJ, Ziebe S, Priskorn L, Juul A. Male Reproductive Disorders and Fertility Trends: Influences of Environment and Genetic Susceptibility. Physiological Reviews. 2016 96:55-97. doi:10.1152/physrev. 00017.2015. Review.
6. The EFSA Journal 284, 1-137, 2005

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