Registration Dossier

Administrative data

Description of key information

Key data were identified to evaluate the acute oral and inhalation toxicity potential of di-tert-nonyl polysulfide. Key read across data were identified to evaluate the acute dermal toxicity potential of di-tert-nonyl polysulfide. The important parameters of interest are presented below:
• Acute oral LD50: 19,550 mg/kg bw
• Acute inhalation LC50 (aerosol): >15.5 mg/L
• Acute dermal LD50: >2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Acute Oral Toxicity

 

One key study in rats was identified to evaluate the acute oral toxicity potential of di-tert-nonyl polysulfide.

 

In a key acute oral toxicity study (Rondot, 1979; Klimisch score = 2), male and female Sprague-Dawley rats (5/sex/dose) were orally administered (via gavage) TPS 37 at doses of 16,000, 18,000, 22,000, and 24,000 mg/kg and observed for 14 days.

 

Mortality was seen at each dose tested with 20%, 30%, 60%, and 80% death observed at the 16,000, 18,000, 22,000, and 24,000 mg/kg dose levels, respectively. One hour after treatment, animals dosed at 16,000 and 18,000 mg/kg were observed to be experiencing spontaneous activity in lower limbs, apathy, piloerection, prostration, and slight closing of the palpebral slit. These same symptoms were 6 hours post-exposure. On day 3 post-exposure, surviving animals appeared to be symptom free and functioning normally. Rats treated at 22,000 and 24,000 mg/kg exhibited a severe reduction in spontaneous activity, prostration, and staggering step. Similar signs were observed 24 hours later in addition to diarrhea. On day 2 post-exposure, piloerection was observed in surviving animals. On day 3, test animals administered 22,000 mg/kg TPS 37 showed signs of recovery while rats administered 24,000 mg/kg TPS 37 were observed to have a distended abdomen. Based on the mortality observed through the study period, the acute oral LD50 was determined to be 19550 mg/kg bw in male and female rats.

 

Supporting read across data is available from a guideline (OECD 401) study conducted in rats (Clouzeau, 1992; Klimisch score = 1) orally exposed (via gavage) to di-tert-butyl polysulfide at single doses of 2000 mg/kg bw. A slight to well-defined decrease in spontaneous activity and respiratory difficulties were observed in all animals within the hours following treatment. From day 2 to day 15, the general behaviour returned to normal and no mortality was observed through the study period. The body weight gain of the animals was not affected by treatment and a macroscopic examination at the end of the study revealed no abnormalities in treated animals of either sex. Under these experimental conditions, the LD0 of di-tert-butyl polysulfide was determined to be ≥2000 mg/kg bw.

 

Acute Inhalation Toxicity

 

One key study in rats was identified to evaluate the acute inhalation toxicity potential of di-tert-nonyl polysulfide.

 

In a key acute inhalation toxicity study (Delhomme and Traynard, 1979; Klimisch score = 2), Sprague-Dawley rats (10/sex) were exposed (whole body) to aerosols of di-tert-nonyl polysulfide for 4 hours at a concentration of 15.5 mg/L. Animals were subsequently observed for a period of 14 days.

 

Clinical signs observed after removal of test animals from the chamber included wet fur and flight-like response. The muzzle of test animals appeared to be slightly irritated but animals appeared to return to normal activity within 15 minutes of being removed from the chamber. On day 1 post-exposure, closed palpebral slit, cyanosed eyes, polypnea, and bronchial obstruction were observed. One male rat died on day 2 but by day 4 all surviving animals appeared to be normal. Necroscopy indicated that lungs were clear. In the absence of other treatment-related signs of systemic toxicity, the acute inhalation LC50 was determined to be >15.5 mg/L.

Acute Dermal Toxicity

 

No key data were identified for di-tert-nonyl polysulfide. However, key read across data were identified for di-tert-butyl polysulfide and di-tert-dodecyl polysulfide (structural analogues of di-tert-nonyl polysulfide).

 

In a key read across acute dermal toxicity study (Clouzeau, 1993; Klimisch score = 1) di-tert-butyl polysulfide (TPS 44) was dermally administered to Sprague-Dawley rats (5 /sex) under semi-occlusive wrap at a dose of 2000 mg/kg for a period of 24 hours. The animals were checked for clinical signs, mortality and body weight gain for a period of 14 days following the single application of the test substance and necropsy was performed on each animal sacrificed at the end of the study period. The general behaviour and body weight gain of the animals were not affected by treatment with the test substance. No mortality was observed at 2000 mg/kg. A macroscopic examination revealed no abnormalities in the animals sacrificed at the end of the study. Based on the lack of adverse treatment-related effects observed, the acute dermal LD0 of TPS 44 was determined to be >2000 mg/kg.

Acute Toxicity: Other Routes

 

In a key acute toxicity study (Rondot, 1979; Klimisch score = 2), Sprague-Dawley rats (5/sex/dose) were administered a single intraperitoneal dose of di-tert-nonyl polysulfide (TPS 37) at doses of 3500, 4500, or 6000mg/kg and subsequently observed for a period of 14 days.

 

Mortality was observed in male and female rats treated at all doses. One hour after treatment with 3500 mg/kg TPS 37, reduced spontaneous activity, apathy, prostration, piloerection, and slight closing of the palpebral slit was observed. These signs persisted through 6 hours and only piloerection was observed on day 2 post-exposure. On day 3, piloerection was observed in one female rat while all other surviving animals appeared normal. One hour after treatment with 4500 mg/kg TPS 37, low spontaneous activity, apathy, prostration, piloerection, and closing of the closing of the palpebral slit was observed. Six hours after treatment, moribund animals were found. Recovery of survivors began the next day. The same observations were made when the treatment dose was 6000 mg/kg, but symptoms were more pronounced. The intraperitoneal LD50 was determined to be 3828 mg/kg bw.


Justification for selection of acute toxicity – oral endpoint
In one key acute oral toxicity study, the LD50 of TNPS was determined to be 19550 mg/kg. In a supporting read across study the LD50 of a related structural analogue was > 2000 mg/kg.

Justification for selection of acute toxicity – inhalation endpoint
In a key acute inhaltion toxicity study, the LC50 of TNPS aerosol was determined to be > 15.5 mg/L.

Justification for selection of acute toxicity – dermal endpoint
In 'read across' acute dermal toxicity studies with two related structural analogues, the LD50 was determined to be > 2000 mg/kg.

Justification for classification or non-classification

Based on evaluation of the acute oral, dermal, and inhalation toxicity data discussed above, di-tert-nonyl polysulfide does not meet the criteria for classification as an acute oral, dermal, or inhalation toxicant under EU Dangerous Substances Directive 67/548/EEC or CLP EU Regulation 1272/2008 because the LD50 and LC50 values reported for this substance exceed the upper discriminating threshold limits for classification defined in the regulations.