3-(methylthio)propionaldehyde

Acute Toxicity: other routes

Administrative data

Endpoint:

acute toxicity: other routes

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Remarks:

(limited documentation, purity of test material not indicated, no details on animals and environmental conditions)

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted 09 Oct. 2017

Deviations:

yes

Remarks:

no experimental details given, no body weight and no clinical signs recorded, no scoring according to Draize criteria, no data on analytical purity, no details on animals and environmental conditions, occlusive dressing

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: OFA

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 250 g (males) and 200 g (females)

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 h

Doses:

0.25, 0.5, 1, 2 mL/kg bw corresponding to 259, 518, 1036 and 2072 mg/kg bw

No. of animals per sex per dose:

0.25, 0.5 and 1 mL/kg bw (corresponding to 259, 518, 1036 mg/kg bw): 5
2 mL/kg bw (corresponding to 2072 mg/kg bw): 10

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes

Sex:

male/female

Dose descriptor:

LD50

Effect level:

673 mg/kg bw

Based on:

test mat.

Remarks on result:

other: corresponding to 0.65 mL/kg bw, dosel levels in mg/kg bw calculated with a density of 1036 mg/mL

Mortality:

0.25 mL/kg bw corresponding to 259 mg/kg bw: 0/5 males and 1/5 females died within 24 h.
0.5 mL/kg bw corresponding to 518 mg/kg bw: 0/5 males and 4/5 females died within 24 h.
1 mL/kg bw corresponding to 1036 mg/kg bw: 4/5 males and 2/5 females died within 24 h.
2 mL/kg bw corresponding to 2072 mg/kg bw: 10/10 males and 10/10 females died within 2 h.

Clinical signs:

Severe oedema was observed after 24 h. Scab formation was observed that detached from the skin between 4 to 15 days post application.

Body weight:

No information available

Gross pathology:

No significant macroscopic abnormalities were observed.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

CLP: Acute Dermal 3, H311 according to Regulation (EC) No. 1272/2008

Cross-reference 2

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

adopted 07 Sep 2009

Deviations:

yes

Remarks:

no experimental details, no information on analytical purity, no details on test animals, no information on frequency of observations, body weights not recorded, particle size distribution not determined, analytical concentrations not given for all doses

GLP compliance:

no

Test type:

traditional method

Limit test:

no

Species:

mouse

Strain:

other: Oncins France Strain 1 (OF1)

Sex:

not specified

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

1.2, 6.0, 12 and 24 mL/m3, corresponding to 1.24, 6.22, 12.42 and 24.86 mg/L

No. of animals per sex per dose:

8 / dose group (sex unspecified)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes

Sex:

not specified

Dose descriptor:

LC50

Effect level:

> 6.22 - < 12.43 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: corresponding to > 6 < 12 mL/mg3 air (nominal concentration), dose levels in mg/L air were calculated as follows: [dose level in ppm x molecular weight] / 24,200)

Mortality:

1.2 mL/m3 air (corresponding to 1.24 mg/L air): no mortality occurred
6.0 mL/m3 air (corresponding to 6.22 mg/L air): 2/8 animals died (after 2 h of exposure and on Day 1)
12 mL/m3 air (corresponding to 12.43 mg/L air ): 8/8 animals died (within 3 h during exposure)
24 mL/m3 air (corresponding to 24.86 mg/L air): 8/8 animals died (within the first hour of exposure)

Clinical signs:

other: Irritation of eyes and nasal mucosa was observed at the beginning of exposure.

Body weight:

No information on body weight available

Gross pathology:

There were no macroscopic lesions observed.

Interpretation of results:

study cannot be used for classification

Cross-reference 3

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

adopted 07 Sep 2009

Deviations:

yes

Remarks:

no experimental details, no information on analytical purity, no details on test animals, no information on frequency of observations, body weights not recorded, particle size distribution not determined, analytical concentrations not given for all doses

GLP compliance:

no

Test type:

traditional method

Limit test:

no

Species:

rat

Strain:

other: Oncins France Strain A (OFA)

Sex:

not specified

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 200 - 300 g

Route of administration:

inhalation: vapour

Details on inhalation exposure:

The rats were placed into a 500 L inhalation chamber . They were exposed to the test item as vapour in air at a flow rate of 1m3/h. A saturation of the atmosphere with the test item vapour was noticed at the highest concentrations tested (e.g. 12 and 24 mL/m3)

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

1.2, 6.0, 12, 24 mL/m3, corresponding to 1.24, 6.22, 12.42 and 24.86 mg/L

No. of animals per sex per dose:

1.2 and 6.0 mL/m3 (corresponding to 1.24 and 6.22 mg/L air): 10 / dose group (sex unspecified)
12 and 24 mL/m3 (corresponding to 12.43 and 24.86 mg/L air): 8 / dose group (sex unspecified)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes

Sex:

not specified

Dose descriptor:

LC50

Effect level:

> 1.24 - < 24.86 mg/L air (nominal)

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: corresponding to > 12 < 24 mL/m3 air (nominal), dose levels in mg/L air were calculated as follows: [dose level in ppm x molecular weight] / 24,200)

Mortality:

1.2 mL/m3 air: no mortality occurred
6.0 mL/m3 air: no mortality occurred
12 mL/m3 air: no mortality occurred
24 mL/m3 air: 8/8 animals died (6/8 died after 2-3 h of exposure, 2/8 died during post-exposure days 2 and 4)

Clinical signs:

other: Irritation of eyes and nasal mucosa was observed at the beginning of exposure.

Body weight:

No information on body weight available.

Gross pathology:

There were no macroscopic lesions observed.

Other findings:

The test atmosphere was saturated with test item vapour at ≥ 12 mL/m3 air, corresponding to ≥ 12.43 mg/L air. Below the saturation limit (at 1.2 and 6 mL/mg air, corresponding to 1.24 and 6.22 mg/L air) no mortality was expected.

Interpretation of results:

study cannot be used for classification

Cross-reference 4

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted 09 Oct 2017

Deviations:

yes

Remarks:

no details on animals and environmental conditions, post observation period only 7 days, purity not indicated

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.5 kg
- Housing: Individually in cages measuring 600 x 540 x 315 cm
- Diet: granulated rabbit food (SANDERS), 200 g per rabbit per day
- Water: ad libitum

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL

Duration of treatment / exposure:

6 rabbits: single application of undiluted test item without washing
6 rabbits: single application of undiluted test item with rinsing after 30 seconds following test item instillation

Observation period (in vivo):

7 days
Reading time points: 1 h, 1, 2, 4 and 7 days

Number of animals or in vitro replicates:

12 (6 rabbits with eyes rinsed, 6 rabbits without eyes rinsed)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: with rinsing solution DACRYOSERUM (Laboratories CHIBRET, France) in 6/12 animals
- Time after start of exposure: 4 seconds after test item instillation

SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: ophthalmoscope

Irritation parameter:

chemosis score

Basis:

animal: #1, #2, #3, #4 and #6

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks:

within 7 days

Remarks on result:

other: single application without washout

Irritation parameter:

chemosis score

Basis:

animal #5

Time point:

24/48/72 h

Score:

3.67

Max. score:

4

Reversibility:

not reversible

Remarks:

within 7 days

Remarks on result:

other: single application without washout

Irritation parameter:

chemosis score

Basis:

animal: #7

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

fully reversible within: 4 days

Remarks on result:

other: eye rinsed 4 sec after instillation

Irritation parameter:

chemosis score

Basis:

animal: #8

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 3 days

Remarks on result:

other: eye rinsed 4 sec after instillation

Irritation parameter:

chemosis score

Basis:

animal: #9

Time point:

24/48/72 h

Score:

2.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: eye rinsed 4 sec after instillation

Irritation parameter:

chemosis score

Basis:

animal: #10

Time point:

24/48/72 h

Score:

2.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: eye rinsed 4 sec after instillation

Irritation parameter:

chemosis score

Basis:

animal: #11

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: eye rinsed 4 sec after instillation

Irritation parameter:

chemosis score

Basis:

animal: #12

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 3 days

Remarks on result:

other: eye rinsed 4 sec after instillation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: single application without washout

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: single application without washout

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 4 days

Remarks on result:

other: single application without washout

Irritation parameter:

conjunctivae score

Basis:

animal: #4, #5 and #6

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: single application without washout

Irritation parameter:

conjunctivae score

Basis:

animal: #7

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility not applicable

Remarks on result:

other: eye rinsed 4 sec after instillation

Irritation parameter:

conjunctivae score

Basis:

animal: #8 and #9

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 3 days

Remarks on result:

other: eye rinsed 4 sec after instillation

Irritation parameter:

conjunctivae score

Basis:

animal: #10

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 3 days

Remarks on result:

other: eye rinsed 4 sec after instillation

Irritation parameter:

conjunctivae score

Basis:

animal: #11

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: eye rinsed 4 sec after instillation

Irritation parameter:

conjunctivae score

Basis:

animal: #12

Time point:

24/48/72 h

Score:

1.33

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: eye rinsed 4 sec after instillation

Irritation parameter:

iris score

Basis:

animal: #1 and #5

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: single application without washout

Irritation parameter:

iris score

Basis:

animal: #2, #3, #4 and #6

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: single application without washout

Irritation parameter:

iris score

Basis:

animal: #7

Time point:

24/48/72 h

Score:

0.67

Max. score:

2

Reversibility:

fully reversible within: 3 days

Remarks on result:

other: eye rinsed 4 sec after instillation

Irritation parameter:

iris score

Basis:

animal: #8

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: eye rinsed 4 sec after instillation

Irritation parameter:

iris score

Basis:

animal: #9 and #12

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: eye rinsed 4 sec after instillation

Irritation parameter:

iris score

Basis:

animal: #10

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 4 days

Remarks on result:

other: eye rinsed 4 sec after instillation

Irritation parameter:

iris score

Basis:

animal: #11

Time point:

24/48/72 h

Score:

0.67

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: eye rinsed 4 sec after instillation

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks:

within 7 days

Remarks on result:

other: single application without washout

Irritation parameter:

cornea opacity score

Basis:

animal: #4 and #6

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: single application without washout

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

not reversible

Remarks:

within 7 days

Remarks on result:

other: single application without washout

Irritation parameter:

cornea opacity score

Basis:

animal: #7, #10 and #12

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 4 days

Remarks on result:

other: eye rinsed 4 sec after instillation

Irritation parameter:

cornea opacity score

Basis:

animal: #8

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 2 days

Remarks on result:

other: eye rinsed 4 sec after instillation

Irritation parameter:

cornea opacity score

Basis:

animal: #9

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: eye rinsed 4 sec after instillation

Irritation parameter:

cornea opacity score

Basis:

animal: #11

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 3 days

Remarks on result:

other: eye rinsed 4 sec after instillation

Irritant / corrosive response data:

In rinsed eyes, erythema (conjunctivae redness) was observed in all animals, which fully reversed at the end of the 7 days observation period. In addition, moderate edema (chemosis was observed at the beginning of the observation period, which fully reversed by Day 7. Slight iris lesions and corneal opacity were observed most animals, but the adverse effects were fully reversible in all animals latest by study Day 7.
In non-rinsed eyes, moderate erythema and well defined edema were observed in all animals throughout the whole study period. The adverse effects persistent in all animals until study termination. In addition, slight iris lesions and corneal opacity were observed. Adverse effects on the iris was fully reversible in 4/6 rabbits, but persisted in 2/6 rabbits by study Day 7. Similarly, opacity was reversible in 2/6 rabbits but remained in 4/6 rabbits until study termination.

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

CLP: Eye Dam. 1 H318 according to Regulation (EC) No. 1272/2008.

Cross-reference 5

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

The study was not performed according to modern standards. The dose levels were to high and caused severe local effects. Furthermore the skin was abraded in half of the animals. Purity not stated, too few animals, no statistical evaluation, no details on experimental procedure, type of coverage or frequency of observations, half of the animals were treated at abraded skin, body weight and food consumption were not recorded, few parameters in haematology, clinical chemistry and urinalysis investigated, time of death for individual animals unclear

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: Repeated dose dermal toxicity
- Short description of test conditions: Male and female rabbits (6/sex/group) were dermally treated at 0.2, 0.4, 0.8 and 1.6 mL/kg bw/day for 3 consecutive weeks. The animals were exposed 5 days/week, 6 h exposure per day.
- Parameters analysed / observed: clinical signs, mortality, dermal reactions, gross pathology and histopathology.

Deficiencies when compared to OECD guideline 410:
The study was not performed according to modern standards. The dose levels were too high and caused severe local effects. Furthermore the skin was abraded in half of the animals. The analytical purity of the test material was not stated, too few animals, no statistical evaluation, no details on experimental procedure, type of coverage or frequency of observations, body weight and food consumption were not recorded, few parameters in haematology, clinical chemistry and urinalysis investigated and time of death for individual animals unclear.

GLP compliance:

no

Limit test:

no

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Vehicle:

unchanged (no vehicle)

Details on exposure:

TEST SITE
- Area of exposure: Animals were treated in the dorsal region 24 h after preparation (shaving and scarification).
- Time intervals for shavings or clipplings: The animals were shaved and then closely shaved again. After 24 h, 12 superficial scarifications (3 cm length and spaced 2 cm apart) were made in half of the animals.

REMOVAL OF TEST SUBSTANCE
- Washing: The treated zones were washed with lukewarm water.
- Time after start of exposure: 6 h

TEST MATERIAL
- Amount(s) applied: 0.2, 0.4, 0.8 and 1.6 mL

Duration of treatment / exposure:

21 days

Frequency of treatment:

daily, 5 days/week

Dose / conc.:

0.2 other: mL/kg bw/day

Remarks:

corresponding to 207 mg/kg bw/day

Dose / conc.:

0.4 other: mL/kg bw/day

Remarks:

corresponding to 414 mg/kg bw/day

Dose / conc.:

0.8 other: mL/kg bw/day

Remarks:

corresponding to 829 mg/kg bw/day

Dose / conc.:

1.6 other: mL/kg bw/day

Remarks:

corresponding to 1658 mg/kg bw/day

No. of animals per sex per dose:

6

Control animals:

yes, concurrent no treatment

Details on study design:

- Dose selection rationale: Doses were selected based on the results of a preliminary 4-days range-finding study in which skin reactions were assessed for doses in the range of 1 and 2 mL/kg bw/day.
- No post-exposure recovery group included.

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes

DETAILED CLINICAL OBSERVATIONS: Yes

DERMAL IRRITATION (if dermal study): Yes

BODY WEIGHT: No data

FOOD CONSUMPTION: No

FOOD EFFICIENCY: No

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: before and at the end of treatment
- Parameters examined: leukocyte count
- How many animals: all surviving animals

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: before and at the end of treatment
- Parameters examined: glucose, urea, bilirubin, alkaline phosphatase, serum glutamate pyruvic transferase, serum glutamate oxaloacetic transaminase
- How many animals: all surviving animals

URINALYSIS: Yes
- Time schedule for collection of urine: before and at the end of treatment
- Parameters examined: pH, protein, glucose, ketone bodies, occult blood
- How many animals: all surviving animals

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes

HISTOPATHOLOGY: Yes

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

1.6 mL/kg bw/day: Paraplegia and loss of movement coordination were observed and considered as neurotoxic effects. The animals died within 48 h. The effects were considered adverse and related to treatment.

Dermal irritation:

effects observed, treatment-related

Description (incidence and severity):

A dose-related increase in the intensity of edema was observed. There was no perceptible difference between scarified and non-scarified animals. At 1.6 mL/kg bw/day 6/12 animals showed slight erythema. the observations were considered treatment-related and of toxicological relevance. Despite daily washings the cutaneous alteration induced a formation of a thick crust, cracked and dry, which persisted until study termination.

Mortality:

mortality observed, treatment-related

Description (incidence):

Mortality occured from the second day of dosing in all test item treated groups:
0.2 mL/kg bw/day: 2/12 animals died
0.4 mL/kg bw/day: 3/11 animals died
0.8 mL/kg bw/day: 10/12 animals died
1.6 mL/kg bw/day: 12/12 animals died

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Body weight development was disturbed in the animals which died or had to be sacrificed.

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Description (incidence and severity):

Haematology of surviving animals (0.2 and 0.4 mL/kg bw/day) was not affected by treatment.

Clinical biochemistry findings:

effects observed, non-treatment-related

Description (incidence and severity):

There was a slight, statistically not significant increase of uremia in the non-sacrificed treated animals. The effect was not considered treatment-related.

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not examined

Gross pathological findings:

no effects observed

Neuropathological findings:

effects observed, treatment-related

Description (incidence and severity):

1.6 mL/kg bw/day: Paraplegia and loss of movement coordination were observed and considered as neurotoxic effects. The animals died within 48 h. The effects were considered adverse and related to treatment.

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Description (incidence and severity):

The thickness of the skin (described as oedema) increased immediately after exposure in all animals; it was proportional to the applied dose. At high doses slight erythema was observed as well. Acanthosis, hyperkeratosis and dryness was observed up to the end of the treatment.

Histopathological findings: neoplastic:

not examined

Dose descriptor:

LOAEL

Effect level:

ca. 0.2 other: mL/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

dermal irritation

mortality

Remarks on result:

other: corresponding to 207 mg/kg bw/day

Critical effects observed:

not specified

Conclusions:

The test item repeatedly applied by cutaneous administration induced skin necrosis at all tested dose levels. At the highest dose (1.6 mL/kg bw/day) death occurred between study Day 2-4. Clinical signs at this dose level included paralysis and motion disorders. No clinical signs were seen at the lower dose levels. A death occurred also in the lowest dose group, a NOAEL could not be determined.

Cross-reference 6

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to same study

Qualifier:

equivalent or similar to guideline

Guideline:

other: Draize test

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted 28 Jul 2015

Deviations:

yes

Remarks:

24 h instead of 4 h application, occlusive instead of semi-occlusive application, no details on animals and environmental conditions, reading time points 24 and 72 h only, test item administration application onto abraded and to intact skin area

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.5 - 3.5 kg
- Housing: Individually in cages measuring 600 x 540 x 315 cm
- Diet: granulated rabbit food (SANDERS), 200 g per rabbit per day
- Water: ad libitum

Type of coverage:

occlusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.5 g

Duration of treatment / exposure:

24 h

Observation period:

3 days
Reading time points: 24 and 72 h

Number of animals:

6

Irritation parameter:

erythema score

Basis:

animal: #1, #3, #4, #5 and #6

Time point:

other: 24/72 h

Score:

0.5

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility not applicable

Irritation parameter:

edema score

Basis:

animal: #1 and #3

Time point:

other: 24/72 h

Score:

1.5

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal: #2, #5 and #6

Time point:

other: 24/72 h

Score:

1

Max. score:

4

Reversibility:

not reversible

Irritation parameter:

edema score

Basis:

animal: #4

Time point:

other: 24/72 h

Score:

0.5

Max. score:

4

Reversibility:

not reversible

Irritant / corrosive response data:

Barely perceptible erythema (score 0.5) was observed in 5/6 rabbits, which was fully reversible in all animals within 72 hours after test item instillation. Barely perceptible edema (score 0.5) was observed in 1/6 rabbits, slight edema (score 1) in 3/6 rabbits and slight to well defined edema (score 1.5) was observed in 2/6 rabbits and remained unreversible until study termination 72 hours after test item instillation.

Interpretation of results:

study cannot be used for classification

Conclusions:

The test conditions (24 h exposure under occlusive conditions) may have led to more detrimental skin reactions than those specified in current guidelines. In the 3-days observation period the reversibility of the local skin reactions could not fully be assessed.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1975

Report date:

1973

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

- Principle of test: Acute toxicity after intraperitoneal injection in rats
- Short description of test conditions: 5 rats/sex received a single intraperitoneal injection
- Parameters analysed / observed: Mortality, clinical signs, gross necropsy

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

3-(methylthio)propionaldehyde

EC Number:

221-882-5

EC Name:

3-(methylthio)propionaldehyde

Cas Number:

3268-49-3

Molecular formula:

C4H8OS

IUPAC Name:

3-(methylthio)propionaldehyde

Test animals

Species:

rat

Sex:

male/female

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

water

Doses:

420, 210, 105 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 300 mg/kg bw

Based on:

test mat.

Mortality:

105 mg/kg bw: no mortality occurred.
210 mg/kg bw: no mortality occurred.
420 mg/kg bw: 4/5 males and 5/5 females died within 1 hour post injection.

Clinical signs:

The only clinical symptom that was reported consisted of a pronounced prostration.

Gross pathology:

Gross necropsy revealed no macroscopic findings.

Applicant's summary and conclusion

Conclusions:

The acute lethal dose after intraperitoneal injection in rats was 300 mg/kg bw.