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Key value for chemical safety assessment

Effects on fertility

Description of key information

Both a reproductive screening toxicity study and a 90-day repeated dose toxicity study with read-across
substance Tin sulfide did not demonstrate any obvious adverse effects on the reproductive organs
and function at doses of 100, 300 and 1000 mg/kg bw/day by oral gavage. Therefore Tin sulfide was
considered safe and well tolerated up to the dose of 1000 mg/kg bw/day. The reproductive NOAEL
was defined at 1000 mg/kg. Referring to the results of OECD 421 test, there is no evidence that the
test item is causing any reproductive, developmental as well as teratogenetic toxicity. After detailed
checking "pubmed" source and other sources, even there is no evidence found in epidemiological studies. 

In accordance with column 1 of REACH regulation EC (No) 1907/2006 Annex IX, an extended
one-generation reproductive toxicity study (section, 8.7.3) is required if the 28- or 90-day study  
indicates adverse effects on reproductive organs or tissues. In accordance with column 1 of REACH
regulation EC (No) 1907/2006 Annex IX, an extended one-generation reproductive toxicity study
(section, 8.7.3) was waived.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
High: GLP and guideline compliant study on read-across substance tin sulfide
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

A key reproductive screening toxicity study according to the OECD 421 Test Guideline was conducted with read-across substance Tin sulfide at doses of 100, 300 and 1000 mg/kg bw/day by oral gavage (Valásková, 2010). Males were dosed for a minimum of four weeks and up to and including the day before scheduled kill (this includes a minimum of two weeks prior to mating, during the mating period and, approximately, two weeks post-mating). Females were dosed for a minimum of two weeks prior to mating, during mating and pregnancy and till the third day of lactation. In view of the limited pre-mating dosing period in males, the combination of a pre-mating dosing period of two weeks and subsequent mating/fertility observations, followed by detailed histopathology of the male gonads, is considered sufficient to enable detection of the majority of effects on male fertility and spermatogenesis. Body weight, food consumption, clinical status and macroscopic structure of reproductive organs of treated parental males were unaffected by treatment of the test substance. An absolute weight of pituitary gland was statistically significantly increased in males at the dose level of 1000 mg/kg/day, however in absence of any changes of microscopic structure of the pituitary gland, the effect could be considered not to be of toxicological importance. The test substance had effect on the microscopical structure of the testes without damage of spermiogenesis. Histopathological examination of testes of parental males showed increased incidence of irrelevant changes: degenerations and/or atrophies of germ epithelium and vacuolations of cytoplasm of spermiogonia in males of the dose level 1000 mg/kg/ day. Food consumption, clinical observations, weight and structure of reproductive organs of treated parental females were not significantly affected by treatment of the test substance. Growth of parental females was slightly but insignificantly influenced by the test substance administration: the body weight of females at the dose levels of 300 and 1000 mg/kg/day were slightly decreased during the pregnancy and lactation period. In conclusion, NOAEL for the Reproduction was 1000 mg/kg bw/day, NOEL for the toxic effect on reproduction organs of males was 300 mg/kg bw/day, NOEL for the toxic effect on reproduction organs of females was 1000 mg/kg bw/day.

A key 90- day repeated dose toxicity study in rats daily dosed with Tin sulfide was also available (Slais, 2010) - See endpoint 7.5.1. Tin sulfide to rats was safe and well tolerated up to the dose of 1000 mg/kg bw/day, with NOAEL defined at 1000mg/kg. Histological examination did not elicit any changes on the reproductive organs, therefore fertility was not considered to be adversely affected.

Therefore further examination of reproductive toxicity is not considered to be needed.

 

Based on the similar structural and physicochemical properties of Tin disulfide (target chemical) and tin sulfide (source chemical), as well as the comparable and low toxicological profiles for acute toxicity, local tolerance and genetic toxicity, the results of the reproductive and developmental screening toxicity study with Tin sulfide is considered valid as read-across to Tin disulfide. Therefore no new study has been conducted and current study is considered supporting information for reproductive screening toxicity of Tin disulfide. Further read-across argumentation is provided in a separate document under Section 13.

 

Effects on developmental toxicity

Description of key information

A reproductive screening toxicity study with Tin sulfide in rats did not demonstrate any adverse effects on

the development of the pups at doses of 100, 300 and 1000 mg/kg bw/day by oral gavage. Therefore

read-across substance Tin sulfide was considered safe and well tolerated up to the dose of 1000 mg/kg bw/day.

The developmental NOAEL was defined at 1000 mg/kg.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
High: GLP and guideline compliant study on read-across substance tin sulfide
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

A key reproductive screening toxicity study according to the OECD 421 Test Guideline was conducted with read-across substance Tin sulfide at doses of 100, 300 and 1000 mg/kg bw/day by oral gavage (Valásková, 2010). The OECD 421 Screening Test can be used to provide initial information on possible effects on reproduction and/or development, either at an early stage of assessing the toxicological properties of chemicals, or on chemicals of concern. Males were dosed for a minimum of four weeks and up to and including the day before scheduled kill (this includes a minimum of two weeks prior to mating, during the mating period and, approximately, two weeks post-mating). Females were dosed for at least 2 weeks prior to mating, during mating and gestation up to the third day of lactation.

For the reproductive findings, reference is made to Section7.8.1. For the developmental part of the study, the number of pups, average weight of litter, average body weight of pups on the day of parturition, 1st day after parturition and the 4th day of lactation were insignificantly influenced by the test substance treatment. A slightly lower average number of pups per mother accompanied by lower weight of the litter was detected at the dose levels of 300 and 1000 mg/kg/day but the numbers were not out of historic control. Vice versa, the average weight of pups was higher in treated groups against the control group. Development of pups was not affected by the test substance treatment. Macroscopic abnormalities were only sporadically detected at necropsy of pups and microscopical evaluation of these findings did not reveal relevant pathological effects. In conclusion, NOAEL for the Development of pups was 1000 mg/kg bw/day.

 

Based on the similar structural and physicochemical properties of Tin disulfide (target chemical) and tin sulfide (source chemical), as well as the comparable and low toxicological profiles for acute toxicity, local tolerance and genetic toxicity, the results of the reproductive and developmental screening toxicity study with Tin sulfide is considered valid as read-across to Tin disulfide. Therefore no new study has been conducted and current study is considered supporting information for developmental toxicity of Tin disulfide. Further read-across argumentation is provided in a separate document under Section 13.

 

Justification for selection of Effect on developmental toxicity: via oral route: Supporting study with read across substance. Argumentation on the adequacy of read across between target and source chemical has been documented in a separate document (see Section 13).

Justification for classification or non-classification

Currently no classification and labelling is possible for reproductive and developmental toxicity for Tin disulfide according to EU labelling regulations Commission Directive 93/21/EEC and CLP regulation (No. 1272/2008 of 16 December 2008).