Registration Dossier

Administrative data

Description of key information

Key measured 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. Key values are:

• 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

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Body weights are not taken daily and gross pathology and necropsy were not completed.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: OFA
- Weight at study initiation: 140-170 g
- Housing: cage with dimensions 37.5 x 23.5 x 16 cm

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C
- Humidity (%): 50%
- Air changes (per hr): 6
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Remarks:
none
Doses:
16000, 18000, 22000, and 24000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observations but weighing was only done at the start and end of the experiment
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs and body weight
Statistics:
Probit, Litchfield and Wilcoxon, and Arcsin
Sex:
male/female
Dose descriptor:
LD50
Effect level:
19 550 mg/kg bw
Based on:
test mat.
95% CL:
>= 17 781 - <= 21 495
Mortality:
Groups administered a 22000 mg/kg dose experienced a 70% mortality rate. Groups administered a 16000 mg/kg dose experienced a 20% mortality rate. Groups administered a 18000 mg/kg dose experienced a 30% mortality rate. Groups administered a 22000 mg/kg dose experienced a 60% mortality rate. Groups administered a 24000 mg/kg dose experienced a 80% mortality rate.
Clinical signs:
Clinical signs were generally observed on the day of administration of the dose and one day following. Recovery of clinical signs was observed in most groups 3 days after exposure.
Body weight:
Body weight generally did not change from the initial weighing.
Gross pathology:
Not completed

MORTALITY:

Dose mg/kg

Male

Female

Total

16000

2/5

0/5

2/10

18000

2/5

1/5

3/10

22000

1/5

5/5

6/10

24000

4/5

4/5

8/10



Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 of TPS37 was 19550 (17781-21495) mg/kg.
Executive summary:

In an acute oral toxicity study, groups of male and female Sprague-Dawley rats were given a single gavage dose of TPS 37 at doses of 16000, 18000, 22000, and 24000 mg/kg and observed for 14 days.

 

One hour after treatment with16000 and 18000 mg/kg of TPS 37, rats were observed to be experiencing spontaneous activity in lower limbs, apathy, piloerection, prostration, and slight closing of the palpebral slit. These same symptoms were observed after 6 hours post-exposure. On day 3, the surviving animals appeared to be symptom free and functioning normally. After treatment with22000 and 24000 mg/kg of TPS 37, a severe reduction in spontaneous activity, prostration, and staggering step was observed. Similar signs were observed 24 hours later as well as diarrhoea. On day 2, piloerection was observed in surviving animals. On day 3, test animals administered 22000 mg/kg were beginning to recover. Those administered 24000 mg/kg were observed to have a distended abdomen. The oral LD50 was determined to be 19550 mg/kg bw in males and females.

 

This study received a Klimisch score of 2 and is classified as reliable with restrictions because it is equivalent or similar to OECD guideline 401.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose for cross-reference:
reference to other study
Principles of method if other than guideline:
In the range finding part of the micronucleus assay, 5 male and 5 female rats were treated twice by oral gavage with a dose level of 2000 mg/kg and observed for 24 hours after the last treatment.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River France origin, Saint-Germain-surl’Arbresle; FRANCE
- Age at study initiation: 5 to 10 weeks old
- Weight at study initiation: approximately 200 g
- Assigned to test groups randomly: yes
- Fasting period before study: no
- Housing: animals were housed in polypropylene cages measuring 42.5 x 26.6 x 15 cm, covered by a stainless steel netted lid, in which they will be placed in groups of 3 or 2
- Diet (ad libitum): 801175 RM1(P)DU IRR 9Kgy irradiated from Special Diets Services
(ENGLAND).
- Water (ad libitum): softened by reverse osmosis and filtered on 0.2 µm membrane
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 15
- Air changes (per hr): 20 times per hour
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 24h after the 2nd treatment
- Necropsy of survivors performed: no
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality or clinical signs over 24 h
Mortality:
No mortality was observed.
Clinical signs:
No clinical sign was observed
Body weight:
Not recorded
Gross pathology:
Not performed
Interpretation of results:
GHS criteria not met
Executive summary:

In the range finding part of a micronucleus assay, 5 male and 5 female Sprague-Dawley rats were treated twice by oral gavage with a dose level of 2000 mg/kg of di-t-dodecyl polysulfides (TPS 32) and observed for 24 hours after the last treatment. No mortality or clinical signs were observed.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
Groups of 5-10 male mice were treated by oral gavage with a dose level of 12.5, 25, 30, 40 and 50 ml/kg. The mortality was observed on a 7-day period. Clinical signs and body weight gain were not reported.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
mouse
Strain:
Swiss
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Elevage de Saint Denis de Pile (33), France
- Age at study initiation: no data
- Weight at study initiation: 22 +/-2 g
- Fasting period before study: 16 h
- Housing: 5/cage
- Diet (ad libitum): UAR, France
- Water (ad libitum): tap water
- Acclimation period:no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-1
- Humidity (%): 55
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data
Route of administration:
oral: gavage
Vehicle:
other: undiluted
Doses:
12.5, 25, 30, 40 and 50 ml/kg
No. of animals per sex per dose:
5 or 10
Details on study design:
The mortality was observed on a 7-day period. Clinical signs and body weight gain were not reported.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
ca. 45 mL/kg bw
Based on:
test mat.
Mortality:
Dose (ml/kg) Mortality
12.5 0/5
25 2/5
30 3/10
40 4/10
50 10/10
Clinical signs:
No data
Body weight:
No data
Gross pathology:
No data
Interpretation of results:
GHS criteria not met
Executive summary:

In a pre-guideline study, male Swiss mice (n=40) were dosed with di-t-dodecyl polysulfide. Mortality was observed over a 7-day period; clinical signs and body weight gain were not reported. The LD50 was ca. 45.0 ml/kg bw.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
Not reported
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Iffa Crédo, 69120 L'Arbresle, France
- Age at study initiation: 6-week old
- Weight at study initiation: 182 +/- 15g for the males and 138 +/- 4 g for the females
- Fasting period before study: 18 hours
- Housing: in groups of 5 per sex in polycarbonate cages
- Diet (e.g. ad libitum): Rats - Mice sustenance ref A04 (UAR, France)
- Water (e.g. ad libitum): filtered tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 50 +/- 20
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test substance was administered by oral route to a group of 10 fasted Sprague-Dawley rats (5 males and 5 females). The test substance was administered in its original form at a dose level of 2000 mg/kg at a volume taking into consideration that the specific gravity (SG) of the test substance was 1.007.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
The mortality, general behaviour and body weight gain of the animals were observed for a period of 14 days after the single administration of the test substance. A necropsy was performed on each animal sacrificed at the end of the study.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 000 mg/kg bw
Mortality:
No deaths occurred at the dose level of 2000 mg/kg.
Clinical signs:
A slight to well-defined decrease in spontaneous activity and respiratory difficulties were observed in all animals within the hours following the treatment. From day 2 to day 15, the general behaviour returned was normal.
Body weight:
The body weight gain of the animals was not influenced by the treatment.
Gross pathology:
The macroscopic examination revealed no abnormalities in the animal sacrificed at the end of the study.
Interpretation of results:
GHS criteria not met
Conclusions:
The LD0 of TPS 44 administered by oral route in rats was higher than or equal to 2000 mg/kg.
Executive summary:

The potential acute toxicity of TPS 44 was evaluated in rats according to the recommendations of O.E.C.D. Guideline No. 401 (O.E.C.D., 24th February 1987) for the testing of chemicals administered by oral route and the Principles of Good Laboratory Practice (O.E.C.D., 12th May 1981). TPS 44 was administered by oral route to a group of 10 fasted Sprague-Dawley rats (5 males and 5 females). TPS 44 was administered in its original form at a dose level of 2000 mg/kg at a volume taking into consideration that the specific gravity (SG) of TPS 44 was 1.007. The mortality, general behaviour and body weight gain of the animals were observed for a period of 14 days after the single administration of TPS 44. A necropsy was performed on each animal sacrificed at the end of the study.

A slight to well-defined decrease in spontaneous activity and respiratory difficulties were observed in all animals within the hours following the treatment. From day 2 to day 15, the general behaviour returned was normal. No deaths occurred at the dose level of 2000 mg/kg. The body weight gain of the animals was not influenced by the treatment. The macroscopic examination revealed no abnormalities in the animal sacrificed at the end of the study.

Under these experimental conditions, the LD0 of TPS 44 administered by oral route in rats was higher than or equal to 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
19 550 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
air
Remarks:
none
Duration of exposure:
4 h
Concentrations:
15.5 mg/L
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: sporadically throughout the study (days 1, 3, 7, 14)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, and histopathology
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 15.5 mg/L air
Exp. duration:
4 h
Mortality:
The overall mortality rate was determined to be 10%.
Clinical signs:
other: CLINICAL SIGNS: During exposure: From the very start of the exposure a very dense white fog settles in the chamber and limit the observation of the animals which remain huddled during the exposure. Only a reduction in the reaction to the noises from 45 m
Gross pathology:
The lungs were observed to be clear.

Mortality:

Total Mortality

Day 1

Day 2

Day 3

Day 4

Day 5

Day 6

Day 7

Day 8

Day 9

Day 10

Day 11

Day 12

Day 13

Day 14

Total %

Male

0

1

1

1

1

1

1

1

1

1

1

1

1

1

20

Female

0

0

0

0

0

0

0

0

0

0

0

0

0

0

0

Total

0

1

1

1

1

1

1

1

1

1

1

1

1

1

10



Interpretation of results:
GHS criteria not met
Conclusions:
The inhalation exposure for 4 hours of 10 rats to a nominal concentration of 15.5 mg/L (1082 ppm) TPS 37 induced a mortality of 10%..
Executive summary:

In an acute inhalation toxicity study, 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. Necropsy 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.

 

The study received a Klimisch score of 2 and is classified as reliable with restrictions because the study follows guidelines equivalent of similar to OECD guideline 403.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
15 500 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: IFFA-CREDO, France
- Age at study initiation: 5-7 weeks old
- Mean weight at study initiation: 189-192g for males and 164-166g for females
- Housing: individual housing in stainless steel mesh cages
- Diet (ad libitum): Rat pelleted complete maintenance (UAR, France)
- Water (ad libitum): softened and filtered drinking water
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-3
- Humidity (%): 30-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back
- % coverage: 10%
- Type of wrap if used: wide adhesive and perforated tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes with lukewarm water
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 ml/kg
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
other: yes, distilled water
Details on study design:
- Duration of observation period following administration: 14 days
- Clinical signs and skin reactions: 15 min after administration, then 1, 2 and 4 hours and daily for 14 days
- Body weight: day -1, 1, 8 and 15
- Necropsy of survivors performed: yes
Statistics:
Not appropriate
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
No mortality and no behavioural anomalies were noted following the administration of the product and during the 14 following days. The local tolerance of the product was good: no cutaneous lesions (erythema or oedema) were observed at the site of product application or during the observation period
Body weight:
The body weight gain of the treated animals was not affected by the treatment.
Gross pathology:
No macroscopic abnormality was observed in the animals sacrificed at the end of the observation period.
Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD0 of TPS 32 is higher than 2000 mg/kg.
Executive summary:

In an OECD TG 402 study, Sprague-Dawley rats (n=20; male and female) were dermally exposed to di-t-dodecyl polysulfides (TPS 32). No mortality or behavioural abnormalities were noted following the initial administration of the test substance or during the 14 days following exposure. No cutaneous lesions were observed at the site of application or during the observation period. Body weight gain was not affected by the treatment, and no macroscopic abnormalities were observed in the animals sacrificed at the end of the observation period. The dermal LD0 was > 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

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; pre-dates GLP and therefore it is Klimisch score = 2), male and female Sprague-Dawley rats (5/sex/dose) were orally administered di-tert-nonyl polysulfide (TPS 37) (via gavage) 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 observed 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 diarrhoea. 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 are 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 a limit dose 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 LD0of di-tert-butyl polysulfide was determined to be ≥2000 mg/kg bw.

Two acute oral toxicity studies are available for the analogue substance di-tert-dodecyl polysulfides:

In an acute oral toxicity study, conducted according to OECD TG 423 and in compliance with GLP, an LD50 of >2000 mg/kg bw was determined in rats for di-tert-dodecyl polysulfides based on no observed mortality and no clinical signs for 24 hours after the last treatment (Simar, 2010; Klimisch score = 1).

An acute oral toxicity study conducted in mice with di-tert-dodecyl polysulfides is of low reliability and it was not conducted according to a guideline. The LD50 was concluded to be 45.0 ml/kg bw based on observed mortality whereas no clinical signs were reported (Lauressergues, 1973; Klimisch score = 4).

 

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 nominal 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. Necropsy 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 (Guillot, 1986; Klimisch score = 1; OECD TG 402), Sprague-Dawley rats (n=20; male and female) were dermally exposed to di-t-dodecyl polysulfides (TPS 32). No mortality or behavioural abnormalities were noted following the initial administration of the test substance or during the 14 days following exposure. No cutaneous lesions were observed at the site of application or during the observation period. Body weight gain was not affected by the treatment, and no macroscopic abnormalities were observed in the animals sacrificed at the end of the observation period. The dermal LD0 was > 2000 mg/kg bw.

 

In a supporting 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 LD0of TPS 44 was determined to be >2000 mg/kg bw.

Read across justification

Several criteria justify the use of the read across approach to fill data gaps for di-tert-nonyl polysulfides using di-tert-dodecyl polysulfides as an analogue. Both di-tert-nonyl polysulfides and di-tert-dodecyl polysulfides, are complex mixtures of polysulfides and have similar physiochemical properties. Hence, the toxicological properties of both these substances are also expected to be similar.

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 6000 mg/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 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 CLP Regulation (EC) No 1272/2008 because the LD50 and LC50 values reported for this substance exceed the upper discriminating threshold limits for classification defined in the regulations.