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Description of key information

The LD50 value in the rat derived from the key oral acute toxicity study with 1,3-propanesultone is 100 - 200 mg/kg bw. After 6 h inhalation exposure the LC50 in rats was approximately 1.7 mg/L air. After a single dermal application of 830 mg/kg bw to mice 15% of the animals died (LD15). For the rabbit and guinea pig a dermal LD50 of 660 mg/kg bw and 700 - 1400 mg/kg bw has been reported, respectively.

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:
1964
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not applicable
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
no data
Route of administration:
oral: unspecified
Vehicle:
other: undiluted and 10% in water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 10%
Doses:
50 - 3200 mg/kg bw
No. of animals per sex per dose:
- No of animals: 16 rats
- Sex: not specified
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 100 - < 200 mg/kg bw
Based on:
test mat.
Mortality:
Mortality occured after 2 hours - 1 day.
Clinical signs:
Animals were moderately to very weak.
They showed prostration, salivation, dark eyes, tremor, gasping, diarrhea and convulsions.
Gross pathology:
No abnormalities were found.
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
CLP: Acute Oral 3, H301
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
100 mg/kg bw
Quality of whole database:
Old study but meets generally accepted scientific principles, acceptable for assessment

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study meets generally accepted scientific principles, acceptable for assessment
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
not applicable
Principles of method if other than guideline:
- 3 rats were whole body exposed to the test item (2-3 L/min through an open-end bubbler at 97 °C) for 6 hours
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
not specified
Route of administration:
inhalation
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
Type of exposure:
2-3 L/min through an open-end bubbler at 97 °C (chamber temperature 28-28.5 °C)
Analytical verification of test atmosphere concentrations:
not specified
Duration of exposure:
6 h
Concentrations:
2.14 mg /L (425 ppm)

1.3 mg/L (260 ppm)
No. of animals per sex per dose:
3 rats per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 8 days
- Other examinations performed: clinical signs, body weight
Sex:
not specified
Dose descriptor:
LC100
Effect level:
2.14 mg/L air
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: 2/3 animals died after 24 h, 3/3 animals died in 8 days
Sex:
not specified
Dose descriptor:
LC0
Effect level:
1.3 mg/L air
Based on:
test mat.
Exp. duration:
6 h
Mortality:
After being expsosed to 2.14 mg/L for 6 hours 2/3 animals died after 24 h, 3/3 animals died within 8 days and 0/3 animals died after exposure to 1.3 mg/L.
Clinical signs:
other: At 2.14 mg/L group: Piloerection and vasodilation: after 3 min Blepharism: after 5 min Lacrimation: 25 min At 1.3 mg/L group: Piloerection: after 5 min Vasodilation: after 15 min Blepharism: after 60 min Lacrimation: 80 min
Body weight:
At 1.3 mg/L group:
weight gain of 115 grams on average
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
CLP: Acute Inhal 4, H332
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
1 700 mg/m³
Quality of whole database:
acceptable for assessment

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1976
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study meets generally accepted scientific principles, acceptable for assessment
Qualifier:
no guideline followed
Principles of method if other than guideline:
-The test solutions and solvents were applied to the skin with fine brushes (one application of 25% w/v propane sultone in toluene)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
mouse
Strain:
other: CFI
Sex:
male/female
Details on test animals or test system and environmental conditions:
- mice were bred in specific pathogen- free conditions at Tunstall Laboratory
- six weeks of age at the beginning of treatment
- water and cubed 86S diet (obtained from Grain Harvesters, Wingham, Kent) were provided ad libitum
- mice were individually housed

Type of coverage:
not specified
Vehicle:
other: toluene
Details on dermal exposure:
- the hair on the back was shorn with fine electric clippers before treatment started
- the test solution (0.1 mL) was applied to the dorsal skin using all-glass syringes
Duration of exposure:
- one single application
Doses:
- 25% (w/v) = 25 mg/mouse corresp. to 830 mg/kg bw
No. of animals per sex per dose:
- 48
Control animals:
yes
Details on study design:
The occurence of lethality was observed daily.
Each animal was examined weekly and the size, appearance and position of all skin lesions were recorded.
After 78 weeks, the mice were killed and subjected to a detailed necropsy and a histological examination of skin and the major viscera for the presence of neoplasms. Similar examinations were carried out on animals dying or killed because of ill-health during the experiment, with the exception of those not surviving beyond the first 7 days after exposure.

Sex:
male/female
Dose descriptor:
other: LD15
Effect level:
830 mg/kg bw
Based on:
test mat.
Remarks on result:
other: - during the first 4 days of the study, 12 males and 2 females died (group size: 48 mice each)
Mortality:
- 12 males and 2 females died after 4 days
Interpretation of results:
study cannot be used for classification
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: only result is given without any information on method
Principles of method if other than guideline:
- only result is given without any information on method
GLP compliance:
no
Test type:
standard acute method
Species:
rabbit
Sex:
not specified
Dose descriptor:
LD50
Effect level:
660 mg/kg bw
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
CLP: Acute Dermal 3, H311
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
1964
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study meets generally accepted scientific principles, acceptable for asessment.
Qualifier:
no guideline followed
Principles of method if other than guideline:
- guinea pigs were treated dermally with 0.1 - 20 mL/kg test item
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
guinea pig
Strain:
not specified
Sex:
not specified
Type of coverage:
other: cuff
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
- the undiluted test item was applied dermally (cuff)
Duration of exposure:
no data
Doses:
0.1 - 20 mL/kg (corresponding to appr. 0.14 - 28 g/kg)
No. of animals per sex per dose:
A total of 12 guinea pigs was used (no further information available)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Other examinations performed: clinical signs, body weight
Statistics:
no data
Sex:
not specified
Dose descriptor:
LD50
Effect level:
>= 700 - <= 1 400 mg/kg bw
Based on:
test mat.
Mortality:
Mortality occured between day 1 and 6.
Clinical signs:
The symptoms were described in the report as follows:

"1, 2, 3 days:
Moderate to gross edema and all of patch area and beyond necrotic to 3 erythema or hemorrhagic at perephery.
Animals hypothermic and moderate tremors.

6 days:
Depressed eschar over patch, to 2 erythema at periphery, heavy desquamation at 1 week.

Scattered light to heavy scarring to 2 eschars or heavy black eschar breaking away at edges and little or no hair at 2 weeks. "
Interpretation of results:
Category 3 based on GHS criteria
Conclusions:
CLP: Acute Dermal 3, H311
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
660 mg/kg bw
Quality of whole database:
acceptable for assessment

Additional information

Oral route:

After oral administration of 50 - 3200 mg/kg bw to 16 rats (OTS, 1992), the LD50-value determined was in the range of 100 - 200 mg/kg bw. Signs of toxicity were characterised by the observation that the animals were moderately to very weak and showed prostration, salivation, dark eyes, tremor, gasping, diarrhea and convulsions (key study).

Oral LD50 values in the rat of 157 and 350 mg/kg bw have been reported in the 1,3-propanesultone MAK value documentation (MAK, 1985). The oral LD50 in the mouse is 400 mg/kg bw (OTS, 1992).

Results of a limit test performed to assess the acute oral toxicity of the hydroysis product of 1,3-propansulton (3-hydroxypropanesulphonic acid) in rats are also available. Therefore, a group of ten fasted animals (five males and five females) was given a single oral dose as a solution in distilled water at a dose level of 2000 mg/kg bodyweight. The animals were observed for 14 days after the day of dosing and were then killed and subjected to gross pathological examination. One female was found dead 30 minutes after dosing. Clinical signs of toxicity noted in one male during Days 4 to 13 included distended abdomen, dehydration, emaciation, hunched posture, decreased respiratory rate, gasping, laboured and noisy respiration and tiptoe gait. Surviving animals showed an expected gain in bodyweight during the study except for one male which showed bodyweight loss during the first week and expected gain during the second week of the study. Abnormalities noted at necropsy of the female that died during the study were abnormally red lungs, dark liver, dark kidneys, severe haemorrhage of the gastric mucosa and severe haemorrhage of the small and large intestines. No abnormalities were noted at necropsy of animals that were killed at the end of the study. On the basis of these results, the LD50 of the hydrolysis product was determined to be greater than 2000 mg/kg bw.

Inhalation route:

After acute inhalation exposure to the test item for 6 h, LC0 and LC100-values of 1.3 mg/Lair and 2.14 mg/L air (aerosol) in rats were obtained, respectively (OTS, 1992). Thus, a LC50 (6 h) of approximately 1.7 mg/L air was derived.

Dermal route:

The effects of limited and prolonged dermal exposure of mice to 1,3-propanesultone were investigated with specific reference to the occurrence of skin and systemic neoplasia in a carcinogenicity study (Doak, 1976). After single application of 0.1 mL of a 25 %(w/v) solution of 1,3-propanesultone to CFI mice 12 males and 2 females died (group size: 48 mice each) during the first 4 days of the study. Assuming a mean mouse body weight of 30 g a LD15 value of 830 mg/kg bw can be derived. The available experimental data is not sufficient to establish a LD50 value. A dermal LD50 value in the rabbit of 660 mg/kg bw is given in the 1,3-propanesultone MAK value documentation (MAK, 1985). For the guinea pig a dermal LD50 of 700-1400 mg/kg bw (OTS, 1992) has been reported. A second study with guinea pigs (OTS, 1992) was disregarded as the study does not meet basic scientific principles of acute dermal toxicity testing.

Other routes:

An intravenous and subcutaneous LD50 of 210 mg/kg bw in the rat has been reported by Druckrey et al. (1970).


Justification for classification or non-classification

Based on the available experimental data the following classification of 1,3-propanesultone is proposed:

- Oral route: Acute tox. oral cat. 3 (H301: toxic if swallowed) according to CLP (Regulation 1272/2008/EC)

- Inhalation route: Acute tox. inhal. cat. 4 (H332: harmful if inhaled) according to CLP (Regulation 1272/2008/EC)

- Dermal route: Acute tox. dermal cat. 3 (H311: toxic in contact with skin) according to CLP (Regulation 1272/2008/EC).