Dodecylbenzenesulphonic acid, compound with 2-amino-2-methylpropan-1-ol (1:1)

Endpoint summary

Description of key information

For DDBSA the acute oral LD50 in male/female rats is 775 mg/kg bw. LD50 value is geometric mean between 300 and 2000 mg/kg.

In an acute oral study on AMP in rats, doses exceeding 2800 mg/kg orally resulted in rapid absorption into the circulatory system resulting in gross damage to the liver, kidney, spleen, and respiratory system followed by respiratory collapse. The compound produces irritation to the stomach and duodenum at doses of 2800 mg/kg and greater. The LD50 was calculated to be 2900 mg/kg bw.

The clipped skin on the backs of five male and five female rats was exposed to the sodium salt of DDBSA 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.

AMP was applied at doses of 1000, 1500 or 2000 mg/kg bw under an occluded dressing for 24 hours to the shaved skin of rabbits. At the end of 24 hr exposure, thetreated skin sites were severely irritated and black in color. The sites became necrotic within two to three days and remained necrotic for the 1 4 days. The treated sites had severe eschar formation by the 14th day. The rabbits in the three treatment groups lost body weight over the two-week observation period. The animals in all the treated groups showed no signs of toxicity or abnormal pharmacological behavior. At necropsy the organs in all rabbits were grossly normal. The treated skin sites in all the rabbits were necrotic. In conclusion, AMP is dermally nontoxic (LD50 > 2000 mg/kg), but is a severe skin irritant.

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

Remarks:

the tested substance is AMP one of the components of the compound

Adequacy of study:

key study

Study period:

Not applicable

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: meets generally accepted scientific standards, well-documented, and acceptable for assessment

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Not applicable

GLP compliance:

not specified

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male

Details on test animals or test system and environmental conditions:

The acute oral toxicity of P-1826 (AMP) was determined using young adult male fasted rats.

Route of administration:

oral: gavage

Vehicle:

other: saline

Details on oral exposure:

Five groups of 10 animals each were administered orally a single dose of P-1826 diluted in saline using equal volumes.

Doses:

2200, 2400, 2800, 3600, 4000 mg/kg (440, 480, 560, 720, 800 mg/ml)

No. of animals per sex per dose:

10 male rats/dose

Control animals:

no

Details on study design:

The acute oral toxicity of P-1826 was determined using young adult male fasted rats. Five groups of 10 animals each were administered orally a single dose of P-1826 diluted in saline using equal volumes. Animals were observed closely for four hours and daily thereafter for 14 days.

Statistics:

Not applicable

Preliminary study:

Not applicable

Sex:

male

Dose descriptor:

LD0

Effect level:

2 200 mg/kg bw

Sex:

male

Dose descriptor:

LD50

Effect level:

2 900 mg/kg bw

Remarks on result:

other: + or- 140 mg/kg

Sex:

male

Dose descriptor:

LD100

Effect level:

4 000 mg/kg bw

Mortality:

Doses exceeding 2800 mg/kg orally results in rapid absorbtion into the circulatory system resulting in gross damage to the liver, kidney, spleen, and respiratory system, followed by respiratory collapse. The compound produces irritation to the stomach and duodenum at doses of 2800 mg/kg and greater.

Clinical signs:

other: In life observations included: traces of blood on the nostrils, labored breathing, ataxia, and death due to respiratory collapse.

Gross pathology:

Necropsy findings (animals that died during the observation period): gas in stomach, inflamed and gaseous duodenum, liver and spleen dark, blood clot in heart.Necropsy findings (survivors until a scheduled necropsy): No findings in dose levels less than 2800 mg/kg. At 2800 mg/kg, 3 were grossly normal and 3 had a small amount of gas in the stomach with a slightly inflamed duodenum. At 3600 mg/kg, 1 was grossly normal and 1 was grossly normal except a stomach adhered to the liver.

Other findings:

The following data are reported:LD0 = 2200 mg/kgLD50 = 2900 +/-140 mg/kgLD100 = 4000 mg/kg

Not applicable

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The substance has low acute oral toxicity.

Executive summary:

The acute oral toxicity of P-1826 was determined using young adult male fasted rats. Five groups of 10 animals each were administered orally a single dose of P-1826 diluted in saline using equal volumes. Animals were observed closely for four hours and daily thereafter for 14 days. P-1826 is the code designation for 2-amino-2-methyl-l-propanol. Doses exceeding 2800 mg/kg orally results in rapid absorption into the circulatory system resulting in gross damage to the liver, kidney, spleen, and respiratory system followed by respiratory collapse. The compound produces irritation to the stomach and duodenum at doses of 2800 mg/kg and greater. The LD50 was calculated to be 2900 mg/kg bw.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Remarks:

the tested substance is DDBSA one of the components of the compound

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.

Qualifier:

according to guideline

Guideline:

other: Safepharm Standard Test Method Number 513.01

Principles of method if other than guideline:

A group of three fasted males and three fasted females were treated with the starting dose (2000 mg/kg bw). As the females dosed with 2000 mg/kg bw died, a further three fasted males and three fasted females were treated with the dose level 300 mg/kg bw. The test material was administered orally as a solution in distilled water. The animals were observed 1/2, 1, 2, and 4 hours after dosing and then once daily for up to 14 days. Bodyweights were recorded on Day 0 (day of dosing) and on Days 7 and 14 or at death. At the end of the observation period the surviving animals were killed by cervical dislocation and all animals were subject to gross necropsy.

GLP compliance:

not specified

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

distilled

Details on oral exposure:

The test material was administered orally as a solution in distilled water. The animals were observed 1/2, 1, 2, and 4 hours after dosing and then once daily for up to 14 days.

Doses:

300,2000

No. of animals per sex per dose:

9

Control animals:

yes

Details on study design:

A group of three fasted males and three fasted females were treated with the starting dose (2000 mg/kg bw). As the females dosed with 2000 mg/kg bw died, a further three fasted males and three fasted females were treated with the dose level 300 mg/kg bw. The test material was administered orally as a solution in distilled water. The animals were observed 1/2, 1, 2, and 4 hours after dosing and then once daily for up to 14 days. Bodyweights were recorded on Day 0 (day of dosing) and on Days 7 and 14 or at death. At the end of the observation period the surviving animals were killed by cervical dislocation and all animals were subject to gross necropsy

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

775 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 value is geometric mean between 300 and 2000 mg/kg bw.

Mortality:

Three females were found dead one day after dosing at the 2000 mg/kg bw dose level. There were no deaths at the 300 mg/kg bw dose level.

Clinical signs:

other: No clinical signs of toxicity were noted in animals treated with 300 mg/kg bw.

Gross pathology:

Abnormalities noted at necropsy of animals that died duringthe study were abnormally red lungs, dark liver, and dark kidneys.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 in male/female rats is 775 mg/kg bw. LD50 value is geometric mean between 300 and 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

910 mg/kg bw

Quality of whole database:

Based on a calculation of the ATE

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Remarks:

the tested substance is the sodium salt of DDBSA one of the components of the compound

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: CFY (remote Sprague Dawley origin)

Sex:

male/female

Details on test animals or test system 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:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: undiluted

Mortality:

No mortality was observed exposure to 2000 mg/kg of the undiluted test material.

Clinical signs:

other: 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 detect

Gross pathology:

All terminal autopsy findings were normal.

There were no deaths or signs of a systemic reaction following a single dermal application at 2000 mg/kg bw. Well defined or slight erythema and slight oedema were observed at all test sites after removal of the occlusive dressing on Day 2. All test sites were entirely covered by scab formation from Day 7. Sloughing from the scabbed skin began at various timesbetween Day 7 and Day 12 and was completed before termination. Lowbodyweight gains or loss of body weight were recorded for one male andthree females in Day 8. Two of the same females and a third female alsoshowed low bodyweight gain between Days 8 and 15.

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

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.

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Remarks:

the tested substance is AMP one of the components of the compound

Adequacy of study:

key study

Study period:

Not applicable

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: meets generally accepted scientific standards, well-documented, and acceptable for assessment

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Principles of method if other than guideline:

Pharmacology Lab Protocol

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Species:

rabbit

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

12 Rabbits weighing 3.0 ± 0.5 kg (6 male, 6 female)8 Rabbits weighing 2.5 ± 0.5 kg (4 male, 4 female)

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

1st part of study:12 Rabbits were divided into 3 groups of 4 each (2 male and 2 female per group), and their abdomens were shaved free of hair. The skin of 2 rabbits per group (1 male and 1 female) were further prepared by abrasions. The abrasions were made 2-3 cm apart over the area of exposure with a blunt hypodermic needle without bleeding.Each group of rabbits was treated with either 1000, 1500, or 2000 mg of test material per kg body weight (mg/kg). The desired dose was spread over the prepared abdominal skin area (abraded or smooth as designated). The skin was covered with a gauze and a sheet of impervious rubberized cloth to prevent any loss of the test material. The trunk was further enclosed with a flexible wire screen held in place by tape. The animals were returned to individual cages.After 24 hours of dermal exposure, the bindings and patches were removed and the exposed areas gently cleaned and checked for irritation.2nd part.Upon completion of the 1st part of the study an additional 8 animals (4 male and 4 femal) were prepared in the same way as above, with the exception that all 8 animals were given abraded skin. These animals were then exposed to 2000 mg/kg bw using the same occluded dressings described above. After 24 hours exposure these animals had their dressings removed and the exposed area washed gently and examined for signs of irritation. These animals were also observed for a further 14 days.

Duration of exposure:

24 hours

Doses:

1000, 1500, or 2000 mg of test material per kg body weight (mg/kg) (doses calculated for each animal based on individual bodyweight)

No. of animals per sex per dose:

4 rabbits/dose, then an additional 8 animals at 2000 mg/kg

Control animals:

no

Details on study design:

Rabbits were weighed at the start of the study and at the end of the 14 day observation period.All animals were sacrificed at the end of the study and necropsied to assess gross pathology. There was no Hematology, clinical chemistry or histopathology carried out on any of the animals.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

None

Clinical signs:

other: At the end of the 24 hour exposure period, the intact and abraded treated skin sites were severely irritated and black in color. The sites became necrotic within two to three days and remained necrotic for the 14 days. The treated sites had severe escha

Gross pathology:

At necropsy, all organs in all rabbits were grossly normal. The treated skin sites in all rabbits were necrotic.

Other findings:

Not applicable

Not applicable

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The acute dermal LD50 for P-1826 for the rabbit was >2000 mg/kg. The test material was dermally nontoxic, but was a severe skin irritant.

Executive summary:

P-1826 (AMP, 2-amino-2-methyl-l-proano1) was tested for acute dermal toxicity using 12 rabbits. The Rabbits were split into 3 groups of 4. All rabbits had their abdomens shaved free of hair, 2 animals in each group also had their skin abraded using a blunt hypodermic needle. The test material was applied at doses of 1000, 1500 or 2000 mg/kg bw under an occluded dressing for 24 hours. After the exposure period the rabbits were observed for a further 14 days. Following this first test an additional 8 rabbits were used. The abdomen of each rabbit was shaved and then abraded using a blunt hypodermic needle. These rabbits were exposed for 24 hours to 2000 mg/kg bw AMP and then followed for a further 14 days. A t the end of 24 hr exposure, the intact andabraded treated skin sites were severely irritated and black in color. The sites became necrotic within two to three days and remained necrotic for the 1 4 days. The treated sites had severe eschar forrnation by the 14th day, The rabbits in the three treatment groups lost body weight over the two-week observation period. The animals in all the treated groups showed no signs of toxicity or abnormal pharmacological behavior. At necropsy the organs in all rabbits were grossly normal. The treated skin sites in all the rabbits were necrotic. In conclusion, AMP was dermally nontoxic (LD50 > 2000 mg/kg), but was a severe skin irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

ATE calculation for acute oral toxicity. ratio AMP/DDBSA in substance 1/1. Weight ratio in substance 21/79%.

100/ATE= 21/2900 + 79/775= 0.11 --> ATE ca 910 mg/kg bw

Justification for classification or non-classification

For oral toxicity the substance needs to be classified in accordance with Regulation (EC) No 1272/2008 (CLP) as acute toxic cat 4 (H302). No classification is necessary for dermal toxicity based on the outcome of the studies.