Polysulfides, di-tert-dodecyl

Endpoint summary

Description of key information

Based on a weight of evidence, the oral LD50 of polysulfides, di-tert-dodecyl is estimated to be higher than 2500 mg/kg bw. The dermal LD0 value for polysulfides, di-tert-dodecyl was > 2000 mg/kg bw (the highest dose tested).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Reason / purpose for cross-reference:

reference to other assay used for intermediate effect derivation

Qualifier:

no guideline available

Principles of method if other than guideline:

7-day range finding study.

GLP compliance:

no

Test type:

other: 7-day range finding study

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Doses:

50, 250, 1250, 2500 mg/kg

No. of animals per sex per dose:

4

Control animals:

no

Details on study design:

Clinical signs and mortality were checked twice daily. Food comsumption and body weight were record ed twice a week.Sacrifice and pathology
A complete macroscopic examination was performed on all animals killed at the end of the study. Adrenals, heart, kidneys, liver, spleen, thymus and gonades were weighed on all animals.

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

> 2 500 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured during the treatment period

Clinical signs:

other: Ptyalism was observed in all the males given 1250 or 2500 mg/kg/day and in 2/4 or 3/4 females given 1250 or 2500 mg/kg/day, respectively

Gross pathology:

Thickened and/or translucent wall of forestomach was noted for 3/4 females given 2500 mg/kg/day.
No effect of treatment was observed on organ weights.

Interpretation of results:

GHS criteria not met

Executive summary:

In a non-guideline dose range-finding toxicity study, male and female Sprague-Dawley rats (4/sex/dose were administered 0, 50, 250, 1250, or 2500 mg/kg bw/day of di-t-dodecyl polysulfides by daily gavage for seven days. No mortality occurred during the treatment period. Ptyalism was observed in all males administered 1250 or 2500 mg/kg bw/day, and in 2/4 and 3/4 females administered 1250 and 2500 mg/kg bw/day, respectively. A slightly lower mean food consumption and body weight gain was observed in the males administered 2500 mg/kg/day. A thickened and/or translucent wall of the forestomach was noted for 3/4 females at 2500 mg/kg bw/day. There was no effect of treatment on organ weights.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

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 and clinical signs over 24 h

Mortality:

No mortality was observed.

Clinical signs:

other: No clinical sign was observed

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 and clinical signs were observed.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Qualifier:

according to guideline

Guideline:

other: REACH guidance. Chapter R.6: QSARs and grouping of chemicals

Version / remarks:

May 2008

Principles of method if other than guideline:

T.E.S.T allows you to estimate the value for oral rat LD50 (amount of chemical in mg/kg body weight that causes 50% of rats to die after oral ingestion)

Specific details on test material used for the study:

Canonical SMILES: CC(C(C)(C)C)C(C)(C)C(C)(C)SSSC(C)(C)C(C)(C)C(C)C(C)(C)C

Species:

rat

Route of administration:

oral: unspecified

Sex:

not specified

Dose descriptor:

LD50

Effect level:

20 008 mg/kg bw

Interpretation of results:

GHS criteria not met

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Pre-guideline study, poorly documented

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:

other: 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 conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 500 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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)

Deviations:

no

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 aghesive 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, distillated water

Details on study design:

- Duration of observation period following administration: 14 days
- Clinical signs ans 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:

other: No mortality and no behavioral 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 a

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 behavioral 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 LD₀was > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

Oral route

In a non-guideline dose range-finding toxicity study, male and female Sprague-Dawley rats (4/sex/dose were administered 0, 50, 250, 1250, or 2500 mg/kg bw/day of di-t-dodecyl polysulfides by daily gavage for seven days (Molinier, 1995). No mortality occurred during the treatment period. Ptyalism was observed in all males administered 1250 or 2500 mg/kg bw/day, and in 2/4 and 3/4 females administered 1250 and 2500 mg/kg bw/day, respectively. A slightly lower mean food consumption and body weight gain was observed in the males administered 2500 mg/kg/day. A thickened and/or translucent wall of the forestomach was noted for 3/4 females at 2500 mg/kg bw/day. There was no effect of treatment on organ weights.

 

In the range finding part of a micronucleus assay (Simar, 2010), 5 male and 5 female Sprague-Dawley rats were treated twice by oral gavage with a dose level of 2000 mg/kg of polysulfides, di-tert-dodecyl and observed for 24 hours after the last treatment. No mortality and clinical signs were observed.

 

An oral LD50 in rats of 20008 mg/kg was estimated using the Toxicity Estimation Software Tool (T.E.S.T) of the US EPA (2017).

 

In a pre-guideline study (Lauressergues, 1973), male Swiss mice (n=40) were dosed with polysulfides, di-tert-dodecyl. 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.

 

Dermal route

In an OECD TG 402 study, Sprague-Dawley rats (n=20; male and female) were dermally exposed to polysulfides, di-tert-dodecyl (Guillot, 1986a). No mortality or behavioral 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.

Justification for classification or non-classification

According to the available data and criteria of regulation no. 1272/2008, no classification is warranted for oral, dermal and inhalation acute toxicity.