Mercury

Endpoint summary

Description of key information

Oral:
- key study: NTP (1993)
- supportive data: Jonker (1993)
Dermal:
- Review EuroChlor 2009 (see discussion)
- weight of evidence of two human reports (Barr_1972 and Dyall-Smith_1990), see section 7.10.3
Inhalation:
- Review EuroChlor 2009 (see discussion)
- weight of evidence of three human reports (Ellingsen_2000a,b and Ellingsen 2001), see section 7.10.3

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Dose descriptor:

LOAEL

0.312 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Additional information

Repeated dose toxicity, oral:

Data on repeated dose toxicity by the oral route in animals are available. In a NTP study, mice and rats were administered orally by gavage for 2 weeks, 26 weeks or 2 years. Another nephrotoxicity study with dietary administration over 4 weeks is described. The lowest LOAEL of 0.312 mg HgCl₂/kg bw/d (0.23 mg Hg/kg bw/d) was identified in the 26-week NTP study in rats based on effects on kidney weights and nephropathy. Results from the subsequent 2-year carcinogenicity study in rats revealed the lowest dose level of 2.5 mg/kg bw/d HgCl₂(1.9 mg Hg/kg bw/d) representing also only a LOAEL based on morphological changes of nephropathy.

Repeated dose toxicity, dermal:

However, there is almost no information available on systemic toxicity resulting from repeated dermal exposure of animals. The evaluation of human literature revealed some information about clinical findings in subjects using skin lightening creams containing mercuric ammonium chloride. It could be concluded that an urinary mercury concentration of 29 µg/l (range 0 -90 µg/l) must be regarded as a LOAEL based on established mercury induced nephrotic syndrom.

However, absorption through the skin is very limited[“... a very small amount of mercury (about 2% of what is taken up by the lungs) enters the body through the skin”], and thus systemic toxicity following repeated dermal exposure appears to be not of major concern.

Repeated dose toxicity, inhalation:

The biological effects of long-time low to moderate exposures to metallic mercury vapours under occupational settings were evaluated in depth by EuroChlor (2009):

It was concluded that with the exception of urinary excretion of N-acetyl-beta-D-glucosamidase (NAG) form the proximal tubular kidney cells it seems from the review of scientific literature that effects on the central nervous system are the most sensitive indicator of Hg toxicity. It is considered that the toxic effects from high level exposure are sufficiently well known. Sufficient knowledge for defining reasonably tenable occupational exposure limits also seems to be in place. This is based on recent epidemiological studies on cohorts under current or historical low level exposures. The conclusion of the author of this review, putting a particular emphasis on the latest Ellingsen et al studies encompassing the magnitude of reversibility after cessation or reduction of exposure, there are reasons to support a NOAEL (no adverse effect level) of 30 μg Hg/g creatinine.

Repeated dose toxicity: via oral route - systemic effects (target organ) urogenital: kidneys