Tin sulfide (Sn2S3)

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

A reproduction and development toxicity screening study according to OECD guideline 421 in rats with tin sulfide revealed the following values:

NOAEL for the Reproduction: 1000 mg/kg bw/day,

NOEL for the toxic effect on reproduction organs of males: 300 mg/kg bw/day,

NOEL for the toxic effect on reproduction organs of females: 1000 mg/kg bw/day,

NOAEL for the Development of pups: 1000 mg/kg bw/day.

Based on this information it is considered that also ditin trisulfide reveals no reproduction and developmental toxicity. The calculated NOAEL for reproduction and development is 1106 mg/kg bw/day.

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

Read-Across Justification_SnS and SnS2 to Sn2S3

Reason / purpose for cross-reference:

read-across source

Clinical signs:

effects observed, non-treatment-related

Description (incidence and severity):

Males:
No treatment-related effects were found in treated males during the health condition control.
No relevant clinical changes were observed in males at all dose levels after application of the test substance.
Slight fall of weight ( one male at the dose level of 100 mg/kg/day in the 6th week) and thinner excrements ( one male at the dose of 1000 mg/kg/day in the 1 st week) were observed sporadically in treated males.
Females:
Slight decreases in body weights were sporadically (in 1 or 2 females from the group) recorded in the 3rd week at all groups including control.
In treated females of all dose levels, no signs of disease were found during the check-in, acclimatisation and application period. Treatment-related effects were not detected during health condition control and clinical observation of females ( except of vocalisation in one female at the dose level of 1000 mg/kg/day in the 5th week).

Dermal irritation (if dermal study):

not examined

Mortality:

no mortality observed

Description (incidence):

There were no unscheduled deaths during the study.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

The average animal body weights at all dose levels were relatively balanced with the control group during the whole application period. No statistically significant differences were detected.

Food consumption and compound intake (if feeding study):

no effects observed

Description (incidence and severity):

Males: Average food consumption values of males at all treated close levels were slightly increased against the control group during the whole study. These differences were not dependent on the dose level and therefore not considered relevant.
Fermales:
Females:
Pre-mating period
Average food consumption of treated females was analogous to food consumption of control females.
Pregnancy
Females without parturition (non pregnant or aborted females) were not included in the evaluation of food consumption during pregnancy. Average food consumption of treated females was well-balanced with control females.
Lactation
Only mothers (females with live pups) were included in evaluation of food consumption during lactation period. Average food consumption of treated females was similar to consumption of control females.

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

The effect on the microscopical structure of the testes (sporadic degeneration and/or atrophy of germ epithelium, residual bodies in germ epithelium and vacuolation of cytoplasm of spermiogonia) had no effect on spermiogenesis, thus, were not relevant.

Histopathological findings: neoplastic:

no effects observed

Other effects:

no effects observed

Reproductive function: oestrous cycle:

no effects observed

Reproductive function: sperm measures:

no effects observed

Reproductive performance:

no effects observed

Body weight, food consumption, clinical status and macroscopic structure of reproductive organs of treated parental males were unaffected by treatment of the test substance. A statistically significant difference was detected in the weight of the pituitary gland. An absolute weight of pituitary gland was statistically significantly incrased in males at the dose level of 1000 mg/kg/day. 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 tests 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. However, there were no histopathological findings in testes in a 90-day study on tin sulfide. 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.
Reproduction parameters - number of females achieving pregnancy, number of females bearing live pups and number of females with live pups at day 4 after parturition in treated groups were similar to the control or higher than the control groups. Duration of mating and pregnancy were similar in the control and treated females. Pre-implantation, post-implantation and postnatal losses were relatively well balanced at the treated groups and control group.

Key result

Dose descriptor:

NOAEL

Remarks:

for the REPRODUCTION

Effect level:

1 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Systemic toxicity

Key result

Dose descriptor:

NOEL

Remarks:

toxic effect on reproduction organs

Effect level:

300 mg/kg bw/day

Based on:

test mat.

Sex:

male

Basis for effect level:

organ weights and organ / body weight ratios

histopathology: non-neoplastic

Key result

Dose descriptor:

NOEL

Remarks:

toxic effect on reproduction organs

Effect level:

1 000 mg/kg bw/day

Based on:

test mat.

Sex:

female

Basis for effect level:

reproductive performance

Clinical signs:

no effects observed

Mortality / viability:

no mortality observed

Description (incidence and severity):

One pup of control group and one pup of the dose level 300 mg/kg/day died after birth – in the period 0/1st day - 4th day.
No differences in development of pups were observed at the control group and at all treated groups.
Statistical evaluation was performed on the number of live pups.
The total numbers of live pups (on the day of parturition/1st day after parturition and the 4th day after parturition) were similar at the control and the dose level 1000 mg/kg. At the dose level 100 mg/kg/day the number was higher, and vice versa at the dose level 300 mg/kg/day, it was slightly lower.
Average numbers of pups per litter were well-balanced at the control and the dose level 100 mg/kg/day. At the dose levels 300 and 1000 mg/kg/day, the average number of pups per litter was decreased compared to the control, however they fell within the normal range of historical control data.

Body weight and weight changes:

no effects observed

Description (incidence and severity):

The average weights of the litters and pups at the dose level 100 mg/kg/day were slightly increased against control. At the dose levels of 300 and 1000 mg/kg/day, the average weight of the litter was lower compared to control, but the average body weights of pups were slightly higher compared to control group. No statistically significant changes were found.

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Sexual maturation:

no effects observed

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Description (incidence and severity):

The macroscopical examination was performed in all pups. Sporadic pathologic findings were recorded in pups of the treated and control groups. The number of pups with macroscopic changes was comparable in the control and 100 and 300 mg/kg dosed groups; an increase in livers with marked structure was noted in the 1000 mg/kg dose group.

Histopathological findings:

no effects observed

Description (incidence and severity):

The microscopical examination was performed in the pups with macroscopic changes: susp. hydrocephalus (litter No. 142 at the dose level 300) - no histopathological changes in cranial cavity; dark spot on testis (litter No. 167 at the dose level 1000) - no histopathological changes on testis and epididymis; oversized teeth (litter No. 127 at the dose level 100) – no histopathological changes and marked structure of liver (litter No. 164 and 171 at the dose level 1000) – extramedullary haemopoiesis was recorded (it is a physiological finding in pups).

Behaviour (functional findings):

not examined

Developmental immunotoxicity:

not examined

The number of corpora lutea, implantations, number of pups and accompanied weight of litter were slightly but insignificantly influenced by the administration of the test substance (decrease esp. at dose levels 300 and 1000 mg/kg/day). Sex ratio, average weight of pups and postnatal development of pups were unaffected. Macroscopic abnormalities were described sporadically in pups of all treated and the control groups.

Key result

Dose descriptor:

NOAEL

Remarks:

for the development

Generation:

F1

Effect level:

1 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

viability

clinical signs

mortality

body weight and weight gain

gross pathology

Reproductive effects observed:

not specified

Conclusions:

A reproduction and development toxicity screening study according to OECD guideline 421 in rats with tin sulfide revealed the following values:
NOAEL for the Reproduction: 1000 mg/kg bw/day,
NOEL for the toxic effect on reproduction organs of males: 300 mg/kg bw/day,
NOEL for the toxic effect on reproduction organs of females: 1000 mg/kg bw/day,
NOAEL for the Development of pups: 1000 mg/kg bw/day.
Based on this information it is considered that also ditin trisulfide reveals no reproduction and developmental toxicity. The calculated NOAEL for reproduction and development is 1106 mg/kg bw/day.

Executive summary:

A reproduction and development toxicity screening study according to OECD guideline 421 in rats with read-across substance tin sulfide revealed the following values:

NOAEL for the Reproduction: 1000 mg/kg bw/day,

NOEL for the toxic effect on reproduction organs of males: 300 mg/kg bw/day,

NOEL for the toxic effect on reproduction organs of females: 1000 mg/kg bw/day,

NOAEL for the Development of pups: 1000 mg/kg bw/day.

The irrelevant negative influence of the read-across test substance treatment expressed in males of the highest dose level (limit dose) consisted of an increase in absolute weight of pituitary gland (without histopathological changes) and an effect on the microscopical structure of the testes (sporadic occurrence of degeneration and/or atrophy of germ epithelium, residual bodies in germ epithelium and vacuolation of cytoplasm of spermiogonia) without effect on the spermiogenesis. Moreover, there were no histopathological findings in testes in a 90-day study on tin sulfide. The average number of pups and accompanied weight of the litters varied among groups, but fell withing historical ranges and these differences were not considered to be toxicologically relevant.

Body weight, food consumption, clinical observations, weight of reproductive organs of parental males were not markedly affected by treatment of the test substance. Body weight, food consumption, clinical observations, organ weights and structure of reproductive organs of parental females were also not adversely affected by treatment of the test substance. Reproductive performance - ability of male and female animals to successfully mate and produce viable offspring was unaffected by the test substance treatment. Also sex ratio and development of pups were not changed in treated groups.

Based on this information it is considered that also ditin trisulfide reveals no reproduction and developmental toxicity. The calculated NOAEL for reproduction and development is 1106 mg/kg bw/day.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 106 mg/kg bw/day

Study duration:

subchronic

Species:

rat

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 reproduction and development toxicity screening study according to OECD guideline 421 in rats with read-across substance tin sulfide revealed the following values:

NOAEL for the Reproduction: 1000 mg/kg bw/day,

NOEL for the toxic effect on reproduction organs of males: 300 mg/kg bw/day,

NOEL for the toxic effect on reproduction organs of females: 1000 mg/kg bw/day,

NOAEL for the Development of pups: 1000 mg/kg bw/day.

The irrelevant negative influence of the read-across test substance treatment expressed in males of the highest dose level (limit dose) consisted of an increase in absolute weight of pituitary gland (without histopathological changes) and an effect on the microscopical structure of the testes (sporadic occurrence of degeneration and/or atrophy of germ epithelium, residual bodies in germ epithelium and vacuolation of cytoplasm of spermiogonia) without effect on the spermiogenesis. Moreover, there were no histopathological findings in testes in a 90-day study on tin sulfide. The average number of pups and accompanied weight of the litters varied among groups, but fell withing historical ranges and these differences were not considered to be toxicologically relevant.

Body weight, food consumption, clinical observations, weight of reproductive organs of parental males were not markedly affected by treatment of the test substance. Body weight, food consumption, clinical observations, organ weights and structure of reproductive organs of parental females were also not adversely affected by treatment of the test substance. Reproductive performance - ability of male and female animals to successfully mate and produce viable offspring was unaffected by the test substance treatment. Also sex ratio and development of pups were not changed in treated groups.

Based on this information it is considered that also ditin trisulfide reveals no reproduction and developmental toxicity. The calculated NOAEL for reproduction and development is 1106 mg/kg bw/day.

Justification for selection of Effect on fertility via oral route:

GLP and guideline compliant study on a structural analogous read-across substance

Effects on developmental toxicity

Description of key information

Referring to the results of OECD 421 study on tin sulfide, there is no evidence that tin sulfides in general are causing any developmental as well as teratogenetical toxicity. After detailed checking literature situation, even there is no evidence found in epidemiological studies.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the results of the available studies on tin sulfide, ditin trisulfide is not subject to classification as reproductive toxic according to the criteria of EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No 1272/2008.