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Description of key information

LD50 (oral) > 2000 mg/kg bw
LC50(inhalation) > 87000 mg/m3
LD50(dermal) > 2000 mg/kg bw

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:
key study
Study period:
From May 06 to May 27, 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test conducted according to internationally accepted Guideline and in according to the GLP Principles
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Sex: Nulliparous abd non pregnant female
- Source: Harlan italy Srl
- Age at study initiation: 6 - 7 weeks old rats
- Weight at study initiation: in the range of 165 and 171 g
- Housing: 3 animals per cages during the study 5 animals per cages during acclimatisation (Clear polysulphone H-Temp solid bottomed cages)
- Cage control: Daily inspected and changed as necessary (at least 3 times/week)
- Diet (e.g. ad libitum): ad libitum (laboratory rodent diet: 4RF 18, Mucedola Srl)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days
- Veterinary health check: During acclimation period

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 °C
- Humidity (%): 55 ± 15 %
- Air changes (per hr): Approximately 15 to 20 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.5 % in aqueous solution of carboxymethylcellulose
- Amount of vehicle (if gavage): 10 ml/kg bw
Doses:
2000 mg/kg bw
A first group of 3 female animals was dosed at a level of 2000 mg/kg body weight (Group 1, Step 1). Mortality did not occur. A second group, similarly composed, was then dosed at the same dose level (Group 2, Step 2). No mortality occurred. No further doses were investigated since the objective of the study had been achieved.
No. of animals per sex per dose:
3 female per tested dose per group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred.
Clinical signs:
No abnormalities were observed.
Body weight:
No abnormalities were observed.
Gross pathology:
No abnormalities were observed.

Mortality and clinical signs

No mortality occurred and no clinical signs were observed in the first group of animals initially dosed at 2000 mg/kg bw (Group 1, Step 1) and in the further group of 3 females dosed at the same dose level (Group 2, Step 2).

 

Body weight

Changes in body weight observed during the study were within the expected range for this strain and age of animals.

 

Necropsy

No abnormalities were observed at necropsy examination performed on all animals dosed at 2000 mg/kg (Groups 1 and 2) at the end of the observation period.

Interpretation of results:
not classified
Remarks:
Migrated information acccording to the CLP Regulation (EC n. 1272/2008) Criteria used for interpretation of results: EU
Conclusions:
LD50 > 2000 mg/kg bw
Executive summary:

Method

The test has been conducted according to the EU method B.1 tris, corresponding to the OECD Guideline 423.

The acute toxicity of the substance was investigated following a single oral administration (10 ml/kg in 0.5 % aqueous solution of carboxymethylcellulose) to the Sprague Dawley rat followed by a 14-day observation period.

 

Observations

No mortality occurred and no signs of toxicity were observed in the 6 animals following dosing at 2000 mg/kg bw. These results indicate that the test item, AP 1300 S, did not induce toxic effects in the rat following oral administration of a single dose at a level of 2000 mg/kg bw.

 

Results

The lack of mortality demonstrates the acute toxicity expected (LD50) to be greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
87 000 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

Acute Toxicity: Oral

The test substance was evaluated for its acute oral toxicity potential in rats. The study was performed according to the OECD guideline 423, following oral administration of a single dose to the rat. No mortality occurred during the study and no abnormalities were observed. There was no effect on body weight gain. The gross necropsy conducted at termination of the study revealed no observable abnormalities.

The acute oral LD50 was determined to be greater than 2000 mg/kg bw

Acute Toxicity: inhalation

The evaluation of acute inhalation toxicity has been based on two studies conducted on a structural analogous and on the precursor/metabolite of AP 1300 S.

The first study (Grate Lakes Chemical Corporation (1982), cited in the WHO publication[1]) was performed on the structural analogous Similar Substance 01 (CAS 21850-44-2); the second one (from Sterner (1967)[2], cited in the WHO publication[1]) was performed on the precursor/metabolite of AP 1300 S, Similar Substance 02 (CAS 79-94-7).

The first study has been considered in order to complete the assessment due to the great similarity between Similar Substance 01 with AP 1300 S. Similar Substance 01 shares with AP 1300 S the same structure, except for the fact that Similar Substance 01 presents two dibromobutane functional groups linked to the dibromophenol core, instead the dibromo-methylbutane as in the case of AP 1300 S.

The Similar Substance 02 is a precursor/metabolite of AP 1300 S, therefore the second study has been also considered for the assessment.

The justification for the Read Across approaches has been attached to the Section 13.

Great Lakes Chemical Corporation (1982) – Similar Substance 01

LC50 > 87000 mg/m3 (LC50 > 87 mg/l)

Sterner (1967) – Similar Substance 02

LC0(8h) > 0.5 mg aerosol/litre air

The LC50 value reported for the Similar Substance 01 in the ECHA website is > 24.4 mg/l air

Acute Toxicity: Dermal

The evaluation of acute dermal toxicity has been based on two studies conducted on a structural analogous and on the precursor/metabolite of AP 1300 S.

The first study (Grate Lakes Chemical Corporation (1987), cited in the WHO publication[1]) was performed on the Similar Substance 01 (CAS 21850-44-2); the second (Hardy (1994)[3] cited in the WHO publication[1]) and the third (Grate Lakes Chemical Corporation (1987), cited in the WHO publication[1]) were performed on the precursor/metabolite Similar Substance 02 (CAS 79-94-7).

The first study has been considered in order to complete the assessment due to the great similarity between Similar Substance 01 with AP 1300 S. Similar Substance 01 shares with AP 1300 S the same structure, except for the fact that Similar Substance 01 presents two dibromobutane functional groups linked to the dibromophenol core, instead the dibromo-methylbutane as in the case of AP 1300 S.

The Similar Substance 02 is a precursor/metabolite of AP 1300 S, therefore the second study has been also considered for the assessment.

The justification for the Read Across approaches has been attached to the Section 13.

Great Lakes Chemical Corporation (1987) – Similar Substance 01

LD50 > 20000 mg/kg bw

Hardy (1994) – Similar Substance 02

LD50 > 2000 mg/kg bw

Great Lakes Chemical Corporation (1987) – Similar Substance 02

LD50 > 3160 mg/kg bw

The LD50 value reported for the Similar Substance 01 in the ECHA website is > 2000 mg/kg bw

 

[1]World Health Organization (WHO, Geneva, 1995); Dr. G.J. van Esch “Tetrabromobisphenol A and Derivatived” (Environmental health criteria; 172)

[2] Sterner W (1967) Acute oral toxicity of tetrabromo-bis-phenol A to rats; acute inhalation toxicity study of tetrabromo-bis-phenol A and acute eye irritation study on rabbits of tetrabromo-bis-phenol A. St. Louis, Missouri, International Bio-Research, Inc. (Report to Great Lakes Chemical Corporation, West Lafayette, submitted to WHO by the Brominated Flame Retardant Industry Panel).

[3] Hardy ML (1994) Summary; TBBPA toxicological studies sponsored by Ethyl Corporation. Baton Rouge, Louisiana, Ethyl Corporation (Report submitted to WHO by the Brominated Flame Retardant Industry Panel).


Justification for selection of acute toxicity – oral endpoint
Test conducted according to internationally accepted Guideline and in according to the GLP Principles

Justification for selection of acute toxicity – inhalation endpoint
No selection has been done due to the Weight of Evidence approach.

Justification for selection of acute toxicity – dermal endpoint
No selection has been done due to the Weight of Evidence approach.

Justification for classification or non-classification

According to the CLP Regulation (EC n. 1272/2008), 3.1 Acute toxicity section, substances can be allocated to one of four toxicity categories based on acute toxicity by the oral, dermal or inhalation route according to numeric criteria. Acute toxicity values are expressed as (approximate) LD50 (oral, dermal) or LC50 (inhalation) values or as acute toxicity estimates (ATE).

 

The oral LD50 value was established to be greater than 2000 mg/kg body weight, therefore the test substance is out of any classification limit for acute oral toxicity (oral acute toxicity Category 4: 300 < ATE ≤ 2000 mg/kg bw).

The dermal LD50 value was established to be higher than 2000 mg/kg body weight, which exceeded the highest CLP limit for classification (dermal acute toxicity Category 4: 1000 < ATE ≤ 2000 mg/kg bw).

The inhalation LC50 value was established to be higher than 87 mg/l, which exceeded the highest CLP limit for classification (inhalation acute toxicity Category 4: 1.0 < ATE ≤ 5.0 mg/l).

 

In conclusion, the test substance is non classified for oral dermal and inhalation acute toxicity, according to the CLP Regulation (EC n. 1272/2008).