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Description of key information

The key study examined the oral toxicity of the test substance in rats. Groups of 5 male and 5 female rats were exposed orally via gavage to 0, 1075, 1220, 1360, or 1710 mg/kg of test substance (all doses reported were adjusted from the original for 86% activity). The animals were then monitored for 14 days for mortality and clinical signs. Body weights were measured on days 7 and 14, and necropsies were performed at the end of the study. No effects on body weight were observed, but all animals showed some signs of toxicity. Symptoms beginning about 30 minutes past application included diarrhea, squatting attitude, breathing difficulties, nose bleeding, ataxia, and lethargy. These symptoms had disappeared in surviving animals by 120 hours. In the animals that died before the end of the study, red mucous was seen in the stomach and intestine. In the surviving animals, hyperemia of the stomach was noted, along with abnormalities of the stomach, liver, spleen, kidneys, and the peritoneum. Mortality was seen at all dose levels, with 4 of 10 animals at the lowest dose level dying. All animals at the highest dose level died. The acute oral LD50, when adjusted for active content was 1080 mg/kg. According to EU GHS guidelines, the test substance is a Category IV toxicant.

No study is required for inhalation exposure (data waiving). In accordance with column 2 of REACH Annex VIII-X, in addition to the oral route, for substances other than gases, an acute toxicity study for at least one other route is required. The choice of the second route will depend on the nature of the substance and the likely route of human exposure. As dermal is the most likely route of exposure and acute dermal toxicity data are available, no data gap for inhalation exposure exists.

Dermal toxicity was examined in a study on LAS. The clipped skin on the backs (approximate 10% of the area) of five male and five female rats were exposed to a dose of 2000 mg/kg LAS and kept under an occlusive dressing for 24 hours, then observed for another 14 days after the dressing was removed and the skin washed in warm water. The treated areas were examined daily for signs of dermal irritation and assessed according to the standard scoring system for erythema, eschar and oedema. On day 15 all animals were sacrificed and given a macroscopic post-mortem examination of internal organs. No mortality was observed at exposures to 2000 mg/kg of the undiluted test material. There were no signs of systemic reaction. Well defined or slight erythema and slight oedema were observed at all test sites after removal of the occlusive dressings, and these reactions were unresolved before progressive hardening of the skin was first detected on day 4. All test sites were entirely covered by scab formation from day 7. Sloughing from the scabbed skin began at various times between day 7 and day 12 and was completed before test termination. Therefore, results indicate slight erythema and slight oedema but no acute mortality. The dermal LD50 is > 2000 mg/kg and LAS is not classified for acute dermal toxicity under CLP.

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:
key study
Study period:
Jan. 1, 1984-Feb. 14, 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication/study report which meets basic scientific principles.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann
- Weight at study initiation: 123 g female, 146 g male
- Fasting period before study:
- Housing: 1-5 animals in Makrolon cages,
- Diet (e.g. ad libitum): R10 Alleidiaet fuer Ratten, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 4-8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1 degree C
- Humidity (%): 60 +/- 5
- Air changes (per hr): 15/hr
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 12.5-19.9% in water

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

Doses:
LAS doses of 1075, 1220, 1360, 1710 or a control
Note that all doses are corrected for 86% activity. The original doses were 1250, 1415, 1580 and 1990 mg/kg.
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
Body weight and other signs were measured on days 7 and 14.
Animals were observed for 14 days after dosing.
Necropsies were performed at the end of the study.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 080 mg/kg bw
Based on:
act. ingr.
Mortality:
Virtually all animals died in doses of 1220 mg/kg and above.
Clinical signs:
Symptoms beginning about 30 minutes past application included diarrhea, squatting attitude, breathing difficulties, nose bleeding, ataxia, and lethargy. These symptoms had disappeared in surviving animals by 120 hours.
Body weight:
No effects to body weight were seen.
Gross pathology:
In the animals that died before the end of the study, red mucous was seen in the stomach and intestine. In the surviving animals, hyperemia of the stomach was noted, along with abnormalities of the stomach, liver, spleen, kidneys, and the peritoneum.

Mortality

Dose (mg/kg)

Sex

Mortality

1075

Male

0

Female

4

1220

Male

5

Female

3

1360

Male

4

Female

5

1710

Male

5

Female

5

Interpretation of results:
Toxicity Category IV
Conclusions:
The acute oral LD50 is 1080 mg/kg. According to EU GHS guidelines, the test substance is a Category IV toxicant.
Executive summary:

This study examined the oral toxicity of the test substance in rats. Groups of 5 male and 5 female rats were exposed orally to 0, 1075, 1220, 1360, or 1710 mg/kg of test substance. The animals were then monitored for 14 days for mortality and clinical signs. All animals showed signs of toxicity. Mortality was seen at all dose levels, with 4 of 10 animals at the lowest dose level dying. All animals at the highest dose level died. The acute oral LD50, when adjusted for activity was 1080 mg/kg. According to EU GHS guidelines, the test substance is a Category IV toxicant.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
Feb. 1, 1984-Feb. 21, 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication/study report which meets basic scientific principles.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
Substance tested contained 60% actives
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann, Borchen, Germany
- Weight at study initiation: 111 g female, 121 g male
- Fasting period before study: 16 hours
- Housing: 1-5 animals in Makrolon cages, type III
- Diet (e.g. ad libitum): R10 Alleindiaet fuer Ratten, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 4-8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1 degree C
- Humidity (%): 60 +/- 5
- Air changes (per hr): 15/hr
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 3.16 mL/kg

Doses:
2510, 2835, 3160 mg/kg test substance (Volume: 2.51 - 3.16 mL/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: Clinical signs (occurrence, nature and duration) and time of death were observed up to 6 hours after treatment and daily thereafter, weighing was performed before treatment and on days 1, 7 and 14 after treatment.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 760 mg/kg bw
Based on:
test mat.
95% CL:
2 579 - 2 953
Mortality:
2510 mg/kg: 1 male and 2 females died within 24 hours
2835 mg/kg: 1 male and 4 females died within 24 hours
3160 mg/kg: 5 males and 4 females died within 24 hours
Clinical signs:
All animals showed signs of toxicity. Symptoms beginning about 60 minutes past application included piloerection, diarrhea, squatting attitude, diuresis, ataxia, nose bleeding and slight sedation. These symptoms had disappeared in surviving animals by 6 days.
Body weight:
No effects to body weight were seen.
Gross pathology:
In the animals that died before the end of the study, red mucous was seen in the stomach and intestine. In some of the surviving animals, partial swelling of gastric mucosa and hyperemia of the small intestine was noted and in two animals adhesion of stomach, liver, spleen, and peritoneum was observed.

Mortality

Dose (mg/kg)

Sex

Mortality

2510

Male

1

Female

2

2835

Male

1

Female

4

3160

Male

5

Female

4

Interpretation of results:
not classified
Conclusions:
The acute oral LD50 is 2760 mg/kg. According to EU GHS guidelines, the test substance is not classified.
Executive summary:

This study examined the oral toxicity of the test substance (containing 60% actives) in rats. Groups of 5 male and 5 female rats were exposed orally to 2510, 2835, or 3160 mg/kg of test substance. The animals were then monitored for 14 days for mortality and clinical signs. All animals showed signs of toxicity. Mortality was seen at all dose levels, with 3 of 10 animals at the lowest dose level dying. 9 of 10 animals at the highest dose level died. The acute oral LD50 was 2760 mg/kg. According to EU GHS guidelines, the test substance is not classified.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
Feb. 1, 1984-Feb. 21, 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication/study report which meets basic scientific principles.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
Substance tested contained 65% actives
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann
- Weight at study initiation: 111 g female, 121 g male
- Fasting period before study: 16 hours
- Housing: 1-5 animals in Makrolon cages, type III
- Diet (e.g. ad libitum): R10 Alleindiaet fuer Ratten, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 4-8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1 degree C
- Humidity (%): 60 +/- 5
- Air changes (per hr): 15/hr
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 39.8-50.2% in water

MAXIMUM DOSE VOLUME APPLIED: 5.0 ml/kg

Doses:
1990, 2250, 2510 mg/kg test substance
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: Clinical signs (occurrence, nature and duration) and time of death were observed up to 6 hours after treatment and daily thereafter, weighing was performed before treatment and on days 1, 7 and 14 after treatment.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 190 mg/kg bw
Based on:
test mat.
95% CL:
2 047 - 2 343
Mortality:
1990 mg/kg: 2 male animals died within 28 hours, none of the females died
2250 mg/kg: 2 males and 4 females died within 48 hours
2510 mg/kg: 4 males and all females died within 28 hours
Clinical signs:
All animals showed signs of toxicity. Symptoms beginning about 30 minutes past application included piloerection, diarrhea, squatting attitude, ataxia, tremor, staggering and slight sedation. These symptoms had disappeared in surviving animals by 72 hours.
Body weight:
No effects to body weight were seen.
Gross pathology:
In the animals that died before the end of the study, red mucous was seen in the stomach and intestine. In some of the surviving animals, partial swelling of gastric mucosa and hyperemia of the small intestine was noted and adhesion of stomach, liver, spleen, and peritoneum.

Mortality

Dose (mg/kg)

Sex

Mortality

1990

Male

2

Female

0

2250

Male

2

Female

4

2510

Male

4

Female

5

Interpretation of results:
relatively harmless
Conclusions:
The acute oral LD50 is 2190 mg/kg. According to EU GHS guidelines, the test substance is not classified.
Executive summary:

This study examined the oral toxicity of the test substance (containing 65% actives) in rats. Groups of 5 male and 5 female rats were exposed orally to 1990, 2250 or 2510 mg/kg of test substance. The animals were then monitored for 14 days for mortality and clinical signs. All animals showed signs of toxicity. Mortality was seen at all dose levels, with 2 of 10 animals at the lowest dose level dying. 9 of 10 animals at the highest dose level died. The acute oral LD50 was 2190 mg/kg. According to EU GHS guidelines, the test substance is not classified.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
Feb. 1, 1984-Feb. 15, 1984
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication/study report which meets basic scientific principles.
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Specific details on test material used for the study:
Substance tested contained 75% actives
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: F. Winkelmann
- Weight at study initiation: 102 g female, 108 g male
- Fasting period before study: 16 hours
- Housing: 1-5 animals in Makrolon cages, type III
- Diet (e.g. ad libitum): R10 Alleindiaet fuer Ratten, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 4-8 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 +/- 1 degree C
- Humidity (%): 60 +/- 5
- Air changes (per hr): 15/hr
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 12.5-19.9% in water

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

Doses:
1250, 1580, 1990 mg/kg test substance
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: Clinical signs (occurrence, nature and duration) and time of death were observed up to 6 hours after treatment and daily thereafter, weighing was performed before treatment and on days 1, 7 and 14 after treatment.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 600 mg/kg bw
Based on:
test mat.
95% CL:
1 455 - 1 760
Mortality:
1250 mg/kg: 1 male and 1 female animal died within 24 hours
1580 mg/kg: 2 males and 2 females died within 24 hours
1990 mg/kg: 4 males and 4 females died within 48 hours
Clinical signs:
All animals showed signs of toxicity. Symptoms beginning about 30 minutes past application included piloerection, diarrhea, squatting attitude, disorders of balance, ataxia and slight sedation. These symptoms had disappeared in surviving animals by 72 hours.
Body weight:
No effects to body weight were seen.
Gross pathology:
In the animals that died before the end of the study, red mucous was seen in the stomach and intestine. In some of the surviving animals, partial swelling of gastric mucosa and hyperemia of the small intestine was noted along with adhesion of stomach, liver, and spleen.

Mortality

Dose (mg/kg)

Sex

Mortality

1250

Male

1

Female

1

1580

Male

2

Female

2

1990

Male

4

Female

4

Interpretation of results:
Toxicity Category IV
Conclusions:
The acute oral LD50 is 1600 mg/kg. According to EU GHS guidelines, the test substance is a Category IV toxicant.
Executive summary:

This study examined the oral toxicity of the test substance (containing 75% actives) in rats. Groups of 5 male and 5 female rats were exposed orally to 1250, 1580 or 1990 mg/kg of test substance. The animals were then monitored for 14 days for mortality and clinical signs. All animals showed signs of toxicity. Mortality was seen at all dose levels, with 2 of 10 animals at the lowest dose level dying and 8 of 10 animals at the highest dose level. The acute oral LD50 was 1600 mg/kg. According to EU GHS guidelines, the test substance is a Category IV toxicant.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 080 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Quality of whole database:
Acute Toxicity, inhalation: No reliable data.

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
Study period:
1986
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP laboratory study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: CFY (remote Sprague Dawley origin)
Sex:
male/female
Details on test animals and environmental conditions:
Rats were in a weight range of 210 to 239 g prior to dosing on day 1 and approximately six to eight weeks of age. All the rats were acclimated to the experimental environment for a period of 15 days prior to study initiation. Animals were housed in individual metal cages with wire mesh floors. Standard diet and water were provided ad libitum. Each animal was identified by cage number and ear punching.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Test material was a yellow viscous liquid and was applied to an area clipped with electric clippers (approximately 10% of the area) on the backs of 10 rats (five male, five female) at a dose of 2000 mg/kg. The areas were covered with gauze held in place with an impermeable plastic dressing. At the end of 24 hours the dressings were carefully removed and the treated area of skin washed in warm water and blotted dry with absorbent paper.
Duration of exposure:
24 hr
Doses:
2000 mg/kg (undiluted)

No. of animals per sex per dose:
5 male and 5 female
Control animals:
not specified
Details on study design:
Animals were observed soon after dosing and then at frequent intervals for the remainder of day 1. On subsequent days the animals were observed once in the morning and again at the end of the experimental day. The treated areas were examined daily for signs of dermal irritation and assessed according to the standard scoring system for erythema, eschar and oedema. All animals were observed for 14 days after dosing. On day 15 all animals were sacrificed and given a macroscopic post-mortem examination of internal organs.
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: undiluted
Mortality:
No mortality was observed exposure to 2000 mg/kg of the undiluted test material.
Clinical signs:
There were no signs of systemic reaction. Well defined or slight erythema and slight oedema were observed at all test sites after removal of the occlusive dressings. These reactions were unresolved before progressive hardening of the skin was first detected on day 4. All test sites were entirely covered by scab formation from day 7. Sloughing from the scabbed skin began at various times between day 7 and day 12 and was completed before test termination.
Body weight:
Low bodyweight gains or loss of bodyweight were recorded for one male and three female rats on day 8. Two of the same females and a third female rat also showed low bodyweight gains between days 8 and 15.
Gross pathology:
All terminal autopsy findings were normal.
Interpretation of results:
not classified
Conclusions:
The acute lethal dermal dose was found to be greater than 2000 mg/kg.
Executive summary:

The clipped skin on the backs of five male and five female rats were exposed to the test material under an occlusive dressing for 24 hours and observed for another 14 days. Results indicate slight erythema and slight oedema but no acute mortality. The dermal LD50 is > 2000 mg/kg.

Endpoint conclusion
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Oral Toxicity: A study comparable to OECD guideline 401 found an acute oral LD50 of 1080 mg/kg. According to EU GHS guidelines, the test substance is a Category IV toxicant. The key study examined the oral toxicity of the test substance in rats. Groups of 5 male and 5 female rats were exposed orally via gavage to 0, 1075, 1220, 1360, or 1710 mg/kg of test substance (all doses reported were adjusted from the original for 86% activity). The animals were then monitored for 14 days for mortality and clinical signs. Body weights were measured on days 7 and 14, and necropsies were performed at the end of the study. No effects on body weight were observed, but all animals showed some signs of toxicity. Symptoms beginning about 30 minutes past application included diarrhea, squatting attitude, breathing difficulties, nose bleeding, ataxia, and lethargy. These symptoms had disappeared in surviving animals by 120 hours. In the animals that died before the end of the study, red mucous was seen in the stomach and intestine. In the surviving animals, hyperemia of the stomach was noted, along with abnormalities of the stomach, liver, spleen, kidneys, and the peritoneum. Mortality was seen at all dose levels, with 4 of 10 animals at the lowest dose level dying. All animals at the highest dose level died. The acute oral LD50, when adjusted for active content was 1080 mg/kg.

The supporting studies examined the oral toxicity for various concentrations of the test substance (75%, 65% and 60%) in rats. The studies followed the same test protocol and methods as the key study. The effects and symptoms observed with the key study for the test substance were also observed in the supporting study. The acute oral LD50’s determined for the concentrations were 1600 mg/kg, 2190 mg/kg and 2760 mg/kg for 75%, 65% and 60% actives, respectively.

According to CLP-Regulation, the test substance is a Category IV toxicant (H302: Harmful if swallowed).

Inhalation Toxicity: There is no reliable study on inhalation toxicity. A study on inhalation toxicity is not considered reliable (KR = 3) due to questions over the composition of the tested material. The study is included for completeness.

In accordance with column 2 of REACH Annex VIII-X, in addition to the oral route, for substances other than gases, an acute toxicity study for at least one other route is required. The choice of the second route will depend on the nature of the substance and the likely route of human exposure. As dermal is the most likely route of exposure and acute dermal toxicity data are available, no data gap exists.

Dermal Toxicity:

A study comparable to OECD guideline 402 found an acute lethal dermal dose of greater than 2000 mg/kg. The clipped skin on the backs (approximate 10% of the area) of five male and five female rats were exposed to a dose of 2000 mg/kg LAS and kept under an occlusive dressing for 24 hours, then observed for another 14 days after the dressing was removed and the skin washed in warm water. The treated areas were examined daily for signs of dermal irritation and assessed according to the standard scoring system for erythema, eschar and oedema. On day 15 all animals were sacrificed and given a macroscopic post-mortem examination of internal organs. No mortality was observed at exposures to 2000 mg/kg of the undiluted test material. There were no signs of systemic reaction. Well defined or slight erythema and slight oedema were observed at all test sites after removal of the occlusive dressings, and these reactions were unresolved before progressive hardening of the skin was first detected on day 4. All test sites were entirely covered by scab formation from day 7. Sloughing from the scabbed skin began at various times between day 7 and day 12 and was completed before test termination. Therefore, results indicate slight erythema and slight oedema but no acute mortality. The dermal LD50is > 2000 mg/kg and is not classified for acute dermal toxicity under CLP.

Justification for classification or non-classification