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Administrative data

Description of key information

In a key read across short-term oral repeat dose toxicity study (Elf Aquitaine, 1995; Klimisch score = 1) Sprague-Dawley rats (6/sex/dose) were orally administered (via gavage) di-tert-dodecyl polysulfide (TPS 32) at doses of 50 or 250 mg/kg bw/day for four weeks. An additional 12 rats/sex/dose were similarly administered TPS at doses of 0 or 1000 mg/kg bw/day for a period of four weeks. On completion of the four week exposure period, the first six surviving animals of each sex in the control and high dose group were kept for a two week recovery period. 
No mortality was observed in male or female rats during the treatment or recovery periods. Ptyalism was observed in all animals that were treated at the 1000 mg/kg bw/day dose level. Body weight and food consumption was observed to be similar between animals in the treatment and control groups. Urinalysis, haematology, and clinical chemistry parameters appeared to be unaffected by exposure to TPS 32. No macroscopic abnormalities were observed and microscopic examinations did not reveal any significant treatment-related effects. Organ weights also appeared to be unaffected by treatment. 
Based on the lack of significant adverse treatment-related effects observed in this study, the NOAEL was determined to be 1000 mg/kg bw/day.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral Repeat Dose Toxicity

Short-term Oral Repeat Dose Toxicity:

No key data were identified for di-tert-nonyl polysulfide. However, key read across data was available from di-tert-dodecyl polysulfide, a structural analog of di-tert-nonyl polysulfide.

An OECD TG 407 study was conducted using male and female Sprague-Dawley rats administered 0, 50, 250, or 1000 mg/kg bw/day of di-t-dodecyl polysulfides by daily gavage for 29 days;  a satellite group in the control and high-dose groups were monitored for two weeks for recovery.  Group sizes were 12/sex for the control and 1000 mg/kg bw/day groups, and 6/sex for 50 and 250 mg/kg bw/day groups.   

One female given 1000 mg/kg bw/day was found dead on day 5.  Prior to death, piloerection, hypokinesia, dyspnea and loud breathing were noted.   At macroscopic examination, foamy contents were found in the trachea as well as dilatation and reddish color was noted for the lungs.   No relevant findings were noted at microscopic examination.  One female given 250 mg/kg bw/day was found dead on day 16; however, no clinical signs were observed prior to death.  At macroscopic examination, dilatation with reddish coloration was noted for the lungs.   No relevant findings were noted at microscopic examination.   The probable cause of death of these two females might be regurgitation or misdosing, consequently these mortalities were not considered to be related to test substance toxicity. No deaths occurred during the recovery period.  Ptyalism was observed in all animals of both sexes given 1000 mg/kg bw/day just after treatment.  This finding was considered to be related to the test substance.   During the recovery period, no clinical signs were observed in the high dose group, and no clinical signs were noted in the other groups during the dosing phase of the study.   During the treatment and recovery periods, mean body weights and food consumption were similar between treated and control animals.   With respect to clinical pathology, on week 4, a slightly higher erythrocyte count and hemoglobin concentration (+5% or +6% for males and females, respectively) was noted in animals of both sexes given 1000 mg/kg bw/day.  This was associated with a slightly higher packed cell volume (+7% and +6%, for the males and females, respectively). These differences from controls were not seen after 2 weeks of recovery.  These differences were not considered to be of toxicological significance.   There were no differences in hematology, blood chemistry and urinalysis measurements that were considered to be of toxicological importance.   Higher mean absolute and relative ovary weights were noted in the females, attaining statistical significance for the relative weight in the intermediate dose-level group (absolute: +26%, +5%, respectively for the intermediate and high dose-level groups; relative: +9%, +35%, +13%, respectively, for the low, intermediate and high dose-level groups).   Higher mean absolute and relative kidney weights were noted for the females given 1000 mg/kg bw/day (absolute and relative: +8%), when compared to the respective controls.  This difference was statistically significant for the relative weight only, and was not considered to be of toxicological importance.   Statistically significantly lower mean absolute and relative mandibular lymph node weights were noted in the females given 1000 mg/kg bw/day as compared to the controls.  Because this was not observed following the treatment period, it was not considered to be of toxicological importance.  Statistically significant lower mean absolute and relative thyroid gland weights were noted in the females given 1000 mg/kg bw/day (absolute: -32%; relative: -37%).  As higher mean thyroid weights were noted after the recovery period, this was not considered to be of toxicological importance.  At necropsy, there were no macroscopic findings considered to be of toxicological importance.  Microscopically, minimal to moderate acidophilic globules were found in the cortical tubular epithelium of kidneys in 3/6 males given 50 mg/kg bw/day and in 5/6 males given 250 mg/kg bw/day; minimal to slight acidophilic globules were found in all treated males at 1000 mg/kg bw/day.  These kidney findings were not observed in any males of the control group.   The presence of acidophilic globules in the treated males was considered to be treatment-related.   No evidence of reversibility was found after the recovery period, as minimal to moderate acidophilic globules were found in the cortical tubular epithelium of 5/6 treated males given 1000 mg/kg bw/day versus minimal acidophilic globules in 1/6 control males.   However it was not associated with any degeneration/necrosis of the cortical tubular epithelium. This was considered to be due to the well-known increase in accumulation of sex-linked protein (α2-µglobuline) in the lysosomes of the cortical tubular cells and this species   and sex-related abnormality was considered to be of no toxicological importance (Hard et al., 2009). Few other microscopic findings were noted, and due to their low incidence, the absence of a dose relationship, they were considered to be of no toxicological importance.   

The NOAEL for both males and females was 1000 mg/kg bw/day


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
No treatment related effects in a well conducted, guideline repeat dose toxicity study in rats

Justification for classification or non-classification

In a read-across study with a structurally related analogue substance, the NOAEL was > 1000 mg/kg. These data do not satisfy the criteria for classification for repeat dose systemic toxicity according to CLP [EU Regulation 1272/2008]