2-amino-2-methylpropane-1,3-diol

Endpoint summary

Description of key information

Oral toxicity: key study in rats using APD (category member), 3 supporting studies from Category Members (AEPD and AMPD)
Dermal: key study in rabbits conducted on APD, one supporting study from category member AEPD

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:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Overall reporting of study is limited, but sufficient information to judge on hazard potential

Justification for type of information:

See attached (in chapter 13 of IUCLID) document with the justification for the category/read-across approach.

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1175 (Acute Oral Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

- Name of test material (as cited in study report): APD-1, 3
- Lot/batch No.: 227-124
- Analytical purity: No data

Species:

rat

Strain:

Sprague-Dawley

Sex:

not specified

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Dosing solution was prepared by dissolving 5 g test material per 10 ml water (USP sterile water for injection).

Doses:

5 g/kg bw

No. of animals per sex per dose:

10 animals (sex not indicated)

Control animals:

no

Details on study design:

Animals dosed and then returned to cages for observation until day 14. Bodyweights were determined prior to dosing and on day of sacrifce (prior to euthenasia). All animals necropsied at sacrifice.

Key result

Sex:

not specified

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

4 out of 10

Clinical signs:

other: 10/10 animals displayed piloerection and lethargy

Gross pathology:

Discoloration of the kidneys, liver, spleen and small intestine and signs of hemorrhaging in the stomach observed in the 4 animals that died.

Other findings:

none

Four rats (4/10) died within 24 hours following administration of the Limit Dose of 5 g/kg. Abnormal clinical signs were observed in all (10/10) animals which included piloerection and lethargy. The four animals that died showed abnormal signs at gross necropsy including discoloration of the kidneys, liver, spleen and small intestine and signs of hemorrhaging in the stomach.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test substance, APD-1, 3 LOT #: 227-124, was evaluated for its potential to produce death following oral administration at a dose of 5 g/kg in male and female Sprague- Dawley rats. Based on the mortality (4/10 animals) in the Limit Test, the test substance is not classified for acute oral toxicity.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study is well conducted and well reported. Although no information on GLP compliance, the study appears to have been done in the spirit of GLP.

Justification for type of information:

See attached (in chapter 13 of IUCLID) document with the justification for the category/read-across approach.

GLP compliance:

not specified

Test type:

acute toxic class method

Limit test:

no

Species:

rat

Strain:

other: Cox-SD albino

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

AEPD was administered via gavage in a single aqueous dose solution (≤5 ml per animal).

Doses:

0, 1800, 2500, 3500, and 5000 mg AEPD/kg bw

No. of animals per sex per dose:

10 per sex per dose

Control animals:

yes

Details on study design:

Animals.
The rats used in this study were purchased at least four days before the test and allowed to acclimatize to the laboratory. Only the healthy animals, free of any sign of disease were selected for the study. The selected animals were fasted overnight and then gavaged with a selected dose. Each animal in the group was identified by a number. A card on the outside of a cage was used to identify the Specie, Sex, Test No., Material, Lot No., Dose, Starting and Ending Dates.

Diet:
The animals were fed Purina Certified Rodent Chow . Each utilized lot was identified and dated.
The diet was certified free of contaminants by the suppliers analysis.

Drinking Water:
Tap water was supplied ad libitum.
Every quarter the aninals' drinking water was analyzed to ensure that the levels of contaminants were equal to or less than the recommended levels as per the Primary Drinking water Regulations (40 CFR 141.11, 141.12, 141.14).

Test Material:
The material was tested as supplied. It was suspended in water.

Test procedure:
The test was carried out with 100 animals (50 nales, 50 females).
Treatment Groups: 10 males and 10 females per dose level (Each group represent one dose level) .
Control Group: 10 males and 10 females dose

Observation:
The animals be observed frequently on the day of dosing and daily thereafter for 14 days
Observations to include: signs of toxicity, poisoning, o r pharmacological effects, any unusual behavior and mortality
Body Weight.
Measured and recorded at day 0 , 7, and 14

Necropsy:
All animals which died during the observation period undergo a complete necropsy. The surviving animals sacrificed by ether. All major organs and
the body cavities exmined for gross abnormalities and then discarded. Any ununual observation recorded and reported.

Oral LD50:
Based on the mortality at the different dose levels, the oral LD50 value, 95 percentile confidence limits, slope, and the standard error are estimated
according to the method of Pinney ( P r o b i t Analysis, Cambridge Press. 1979) adapted t o BASIC computer program.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

3 882 mg/kg bw

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

4 571 mg/kg bw

Mortality:

Animals found dead had significant evidence of intestinal hemorrhage

Clinical signs:

other: After oral dosing of >2500 mg AEPD/kg both sexes developed eye squint by 6 hours.

Gross pathology:

At necropsy all animals had lung infection. The remaining organs examined grossly appeared normal.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 in male and female rats was 4571 mg/kg and 3882 mg/kg, respectively, with an average of 4227 mg/kg.

Executive summary:

AEPD production lot (NPP41344) sample was tested in the rats to determine its toxicity and oral LD50 values. After oral dosing at doses >2500 mg/kg, male and female rats developed eye squint by 6 h. The surviving animals were normal by 24 h. The necropsy of the animals found dead during the observation period showed severe intestinal hemorrhage. On day 5 one of the male rats (#1) at 3500 mg/kg was found cannibalized. At 14 day necropsy of the surviving treated and control animals showed lung infection. The other organs in all the animals were grossly normal. The LD50 for males was calculated to be 4571 mg/kg and for females, 3882 mg/kg. AEPD is therefore considered to be of low acute toxicity.

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study is well reported and appears to have been conducted according to current protocols and according to GLP.

Justification for type of information:

See attached (in chapter 13 of IUCLID) document with the justification for the category/read-across approach.

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Remarks:

Not designated in the abstract.

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

- Name of substance: 2-amino-2-ethyl-1,3-propanediol
- CAS No.: 115-70-8
- Purity: 99.4 %
- Characteristics: slightly yellow and transparent viscous liquid, with no contamination or visible foreign substances

Species:

rat

Strain:

other: Crj:CD(SD)IGS

Sex:

female

Details on test animals or test system and environmental conditions:

21 female Sprague-Dawley SPF rats [Crj:CD(SD)IGS, Japan Charles River Co., Atsugi Breeding Center] were obtained at 7 weeks age and quarantined / acclimated for one week in Bozo labs. From observations during quarantine / acclimation, those considered healthy were randomly chosen and assigned to the experiment at 8 weeks age. Weight range was 179 – 211g, within +/- 20% of average values [average: 190g (152 – 228 g)].

Route of administration:

oral: gavage

Vehicle:

water

Doses:

200 and 3000 mg/kg

No. of animals per sex per dose:

Six

Control animals:

no

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No deaths were observed in both administration groups of 300 and 2000 mg/kg bw.

Clinical signs:

other: No abnormalities were observed in the general conditions in both groups of 300 and 2000 mg/kg bw

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No deaths occurred at either dose level, and the lethal dose was estimated to be higher than 2000 mg/kg. No abnormalities were observed in the general conditions or body weights of any animal or at necropsy.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

1995

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Reporting is limited, but sufficient information to judge the hazard potential

Justification for type of information:

See attached (in chapter 13 of IUCLID) document with the justification for the category/read-across approach.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

EPA OTS 798.1100 (Acute Dermal Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

other: Albino

Sex:

male/female

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

24 hours

Doses:

2g/kg bw

No. of animals per sex per dose:

5 male and 5 female

Control animals:

not required

Sex:

male/female

Dose descriptor:

LD0

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

other: Nine out of ten of the animals exhibited slight to defined Erythema. One rabbit also exhibited Edema at the 24 hour scoring.

Gross pathology:

no effects

Other findings:

none

None of the test animals exhibited clinical signs of toxicity and all animals gained weight during the course of the study. Nine out of ten of the animals exhibited slight to defined Erythema. One rabbit also exhibited Edema at the 24 hour scoring. There were no visible lesions noted in any test animals upon gross observation at necropsy.

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material is considered non-toxic according to the procedures listed in the TSCA guidelines, 40 CFR, Part 798.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Additional information

Oral toxicity:

The acute oral toxicity of the members of this category is low. All oral LD50 values in rats are >2000 mg/kg bw. Clinical signs observed in the available studies include lethargy and hunched posture, consistent with discomfort. Gross pathologial signs were consistent with the high pH of these materials (discoloration of the intestines and signs of hemorrhaging in the stomach). Value taken forward to CSR for acute oral toxicity of APD: LD50 >5000 mg/kg bw.

Dermal toxicity:

The acute dermal toxicity of the members of this category is low. The LD50 values from studies in rabbits are >2000 for APD and AEPD. Given the structural similarity it is assumed that the dermal toxicity of AMPD will be consistent with the other members of the category, and therefore also >2000 mg/kg bw. In the available studies, there were no clinical signs of toxicity other than some local effects (erythema/odema) immediatly following dosing. These subsided by the end of the study.

Value taken forward to CSA for APD: dermal LD50 >2000 mg/kg bw

Inhalation toxicity:

No studies are available for the substances in the category. However given the low toxicity via oral and dermal routes it is considered unlikely that these would pose an acute inhalation toxicity hazard. In addition, the vapour pressure of these substances is low, limiting the potential for an acute inhalation exposure to occur.

Justification for classification or non-classification

The LD50 values for oral and dermal routes are >2000 mg/kg bw, therefore no classification for acute toxicity is required according to DSD or CLP.