2,3-bis((2-mercaptoethyl)thio)-1-propanethiol

Endpoint summary

Description of key information

Oral (OECD 401): LD50, rat = 3577 mg/kg bw 
Dermal (OECD 402 limit test): LD50, rabbit > 2000 mg/kg bw 
Inhalation (OECD 403 limit test): LD50, rat >4.8 mg/L

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998 - 1990

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

not specified

Doses:

250, 500, 1000, 2500, 4000 and 5000 mg/kg

No. of animals per sex per dose:

Range-finding Study: 1 animal/sex/dose.
LD50-Determination: 5 animals/sex/dose.

Control animals:

no

Sex:

female

Dose descriptor:

LD50

Effect level:

3 428 mg/kg bw

Based on:

test mat.

95% CL:

2 354 - 4 994

Sex:

male

Dose descriptor:

LD50

Effect level:

3 643 mg/kg bw

Based on:

test mat.

95% CL:

1 779 - 7 458

Sex:

male/female

Dose descriptor:

LD50

Effect level:

3 577 mg/kg bw

Based on:

test mat.

95% CL:

2 651 - 4 826

Mortality:

Male: 1200 mg/kg bw/d; Number of animals: 5; Number of deaths: 0
Male: 2500 mg/kg bw/d; Number of animals: 5; Number of deaths: 2
Male: 5000 mg/kg bw/d; Number of animals: 5; Number of deaths: 3
Female: 1200 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 1
Female: 5000 mg/kg bw; Number of animals: 5; Number of deaths: 4

Clinical signs:

other: Signs seen on the day of dosing in most groups included oral discharge, urinary and fecal staining, soft stool and hypoactivity. Additional signs seen on the day after dosing included nasal discharge and abdominal griping in the 5000 mg/kg dose group only

Gross pathology:

Postmortem examinations of animals which were found dead revealed a variety of changes, primarily in the lungs and gastrointestinal tract. Some animals which were found dead exhibited changes in the stomach and intestine which were suggestive of an irritant and/or corrosive effect (discoloration of walls, the presence of red, tan or black material). Other changes in animals found dead appeared to represent autolytic changes or were the result of ante-mortem stress (testes in the body cavity). Changes in animals killed after 14 days were similar to those seen in control animals in this laboratory killed by carbon dioxide inhalation or were considered to represent normal physiological variation.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The oral toxicity of DMPT in rats is low (LD50 above 3,000 mg/kg/d). The anticipated mean oral LD50 of 3577 mg/kg/d of DMPT allows classification in OECD GHS Toxicity Category IV.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

3 577 mg/kg bw

Quality of whole database:

Reliable quatlity

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:

25-Oct-1989 ¿ 21-May-1990

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

air

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric determination of DMPT

Duration of exposure:

4 h

Concentrations:

The test animals received an average gravimetric exposure concentration of 4.8 mg/l of DMPT with a nominal exposure concentration of 71 mg/l. A total of 340 grams of test substance was used during the exposure. This was considered a maximum attainable exposure level based on pre-study trials. A distribution sample taken during the second hour of exposure demonstrated less than 10% variability compared to the routine sampling point.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

All animals were held for a 21-day post-exposure observation period and received daily detailed physical observations pretest through Day 22, and body weight measurements on days 1, 2, 3, 5, 8, 15 and 22. After the post-exposure period, all animals were sacrificed and a complete gross postmortem examination was conducted.

Sex:

male/female

Dose descriptor:

LC0

Effect level:

4.8 mg/L air (analytical)

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LC0

Effect level:

71 mg/L air (nominal)

Based on:

test mat.

Mortality:

All animals survived the duration of the study.

Clinical signs:

other: Observations noted during exposure were limited to decreased activity and eye closure. Signs exhibited by animals upon removal from the chamber and during the two-hour post-exposure observation period on Day 1 included labored breathing, lacrimation, nasa

Body weight:

Substantial weight losses were observed during the first 2 to 4 days following exposure. Recovery of weight occurred over time and half of the
animals were in excess of their pre-exposure body weight after 2 weeks. Most of the females continued to gain weight during Week 3, however,
Test Week 3 body weights for the males were less than Test Week 2 because of a water system malfunction.

Gross pathology:

Red/brown discoloration of the skin was observed in 5/5 males and 3/5 females. Red/tan discoloration of the lungs and turbinates were observed in 2/5 male animals. The toxicologic significance of the above findings in a single dose group in the absence of a control group and based entirely on gross findings is equivocal. Other postmortem findings which were observed grossly occurred sporadically and were not considered to be related to the test article.

Interpretation of results:

Category 3 based on GHS criteria

Remarks:

Migrated information

Conclusions:

The inhalation toxicity (aerosol study, MMAD 4.0 µm for 4 h of DMPT in Sprague-Dawley rats is considered to be harmful (LC50 ¿ 5.0 mg/l/4h). No mortalities were observed in this study.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LC50

Value:

5 000 mg/m³ air

Quality of whole database:

LC0= 4..8 mg/L
Reliable quatlity

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:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Assessed after consultation with the relevant Authority. Data migrated from NONS (67/548/EEC notification) files provided by Authority contained insufficient information.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Remarks:

No further information was provided in the SNIF file.

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not specified

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Gross pathology:

Effects on organs:
no unusual findings.

Other findings:

Signs of toxicity (local):
One animal had red, tearing eyes for the duration of the exposure period. Apart from this, no test substance -related effects observed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Reliable quatlity

Additional information

Oral:

One study was available to assess the acute oral toxicity of 2,3 -bis((2-mercaptoethyl)thio)-1 -propanethiol (Mitsui 1993, SNIF#001-4.1.11 -01). The study was performed under GLP according to OECD guideline 401. Five male and female Sprague Dawley CDR rats per group were treated with 1200, 2500 and 5000 mg/kg bw. The observed clinical signs included salivation, hyperactivity, diarrhoea in both groups; convulsions and ataxia in the lowest dose group; and stomach cramps in the highest dose group. Some changes in the gastrointestinal tract were observed, these changes were not described in further detail. The animals that died during the study period partly exhibited gastrointestinal damage indicating a local irritating or corrosive effect of the test substance. It is not clear whether the mortality was caused by local or systemic effects of the substance. However, clinical signs like convulsions and ataxia indicate that the substance is bioavailable and also causes systemic adverse effects. Based on the observed mortality, the oral LD50 was considered to be 3577 mg/kg bw.

Inhalation:

The acute inhalation toxicity was evaluated in a GLP-study performed according to OECD guideline 403 (Mitsui 1993, SNIF#001-4.1.20 -01). The study was a limit test, during which five male and 5 female Sprague Dawley CDR rats were treated with the test substance at 4.8 mg/L for 4 hours. The observed clinical signs included difficulty breathing, nasal discharge, tear discharge, salivation and muscle tremor during the exposure. Post-exposure; nasal discharge, difficulty breathing and redness of the skin on the extremities was observed. Since no mortality was observed, the inhalation LD50 was established at > 4.8 mg/L. The test concentration was probably the technical limit concentration, as the limit for classification as acute toxic category 4 is 5 mg/L. However, no additional justification is given for selecting this exposure concentration. Consequently, the LD0 is 4.8 mg/L, as no effect was observed at this exposure level. It was reported in the field 'Remarks' that a follow-up inhalation study with specific neurological assessments and an inhalation study on the metabolism product were performed. As no additional information on these studies was available they can not be assessed.

Dermal:

One acute dermal toxicity study performed under GLP according to OECD guideline 402 was available (Mitsui 1993, SNIF#001 -4.1.30 -01). Five male and 5 female New Zealand White rabbits were exposed to 2,3 -bis((2-mercaptoethyl)thio)-1- propanethiol in a concentration of 2000 mg/kg (limit test) under occlusive conditions for 24 hours. No mortality occurred and the only clinical signs were observed in one animal exhibiting red, tearing, glazed eyes during the exposure period. There were no unusual findings at the terminal autopsy. Therefore, the LD50 was considered to be >2000 mg/kg bw.

Justification for selection of acute toxicity ¿ oral endpoint
Key study

Justification for selection of acute toxicity ¿ inhalation endpoint
key study

Justification for selection of acute toxicity ¿ dermal endpoint
Key study

Justification for classification or non-classification

According to Annex I of DSD (67/548/EC), 2,3 -bis((2-mercaptoethyl)thio)-1 -propanethiol is classified as Xn, R22.

According toAnnex VI of CLP (1272/2008/EC), 2,3 -bis((2 -mercaptoethyl)thio)-1 -propanethiol is classified as Acute tox. 4, H302.

2,3 -bis((2 -mercaptoethyl)thio)-1 -propanethiol should not be classified according to Annex VI of CLP(1272/2008/EC) for acute inhalation toxicity, as the LD0 is very close to the upper classification limit and it is unlikely that the LD50 would >= 5 mg/L. Furthermore, the substance is not classified according to Annex I of DSD (67/548/EC).