Registration Dossier

Administrative data

Description of key information

A formulation of the substance was tested in an acute oral test (limit test at 5000 mL/kg). One of ten animals died. The outcome was an LD50 of >5000 mL/kg, when corrected for purity 2150 mg/kg bw.

For inhalation toxicity an invalid study on a formulation of the substance was available. As the inhalation route is considered not very relevant for exposure this study is not further taken into account.

Dermal toxicity was evaluated for AMP (LD50 >2000 mg/kg bw), but not for PTSA in view of the corrosive effects of this acid. As the substance is a salt of PTSA corrosion is not expected. In view of the outcome of the acute oral toxicity study on the formulation of the study, it is expected that the substance is of low demal toxicity.

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:
weight of evidence
Study period:
1978
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Qualifier:
equivalent or similar to
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Version / remarks:
Acute Toxicity. FHSLA, CFR Title 21, para. 191.1.
Deviations:
yes
Remarks:
no information on body weight gain, no macroscopic examination
Principles of method if other than guideline:
no information on body weight gain, no macroscopic examination
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Weight at study initiation: 200-208 g
- Fasting period before study: 18 hours
- Housing: individually
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS; no data
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
5 mL/kg bw
No. of animals per sex per dose:
10 males
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily for mortality and gross toxicity
- Necropsy of survivors performed: no
Statistics:
NA
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 mL/kg bw
Based on:
test mat.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 150 mg/kg bw
Based on:
act. ingr.
Remarks on result:
other: corrected for purity based on a density of the formulation of 1 mg/cm3
Mortality:
none
Clinical signs:
none observed
Body weight:
no data
Gross pathology:
no data
Interpretation of results:
GHS criteria not met
Conclusions:
The LD50 of the substance is > 2150 mg/kg bw
Executive summary:

The substance (formulation) was tested for acute toxicity in 10 male rats at 5 mL/kg bw. No mortality or signs of toxicity were observed during the 14 -day observation period. The LD50 is >2150 mg/kg bw when corrected for purity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 150 mg/kg bw
Quality of whole database:
the test was perofmed on a formulation and the LD50 was claculated based on the concentration of the substance in the formulation

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:
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:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
equivalent or similar to
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 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:
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 eschar formation by the 14th day. The animals in all treated groups showed no signs of toxicity or abnormal pharmacological behavior.
Body weight:
The rabbits in the three treatment groups lost body weight over the 14 day observation period.
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:
not classified
Remarks:
Migrated informationCriteria 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
2 000 mg/kg bw

Additional information

Justification for classification or non-classification

Based on the considerations above the substance is not to be classified for acute toxicity according to (EC) No 1272/2008 (CLP).