Registration Dossier

Administrative data

Description of key information

Acute Oral toxicity:

- LD50 = 9187 mg/kg bw (OECD 401, Key, rel.2)

- LD50 > 2000 mg/kg bw (OECD 401, Supp, rel.2)

Acute dermal toxicity:

LD50 > 2000 mg/kg bw (OECD 402, Key, rel.2)

Acute inhalation toxicity:

Based on the particle size the inhalatory toxicity test with the solid test article was not possible. Instead an aqueous suspension in deionised water was tested. 1 < LC50(aqueous suspension) < 5 mg/L (OECD 403, GLP, Supp, rel.4). This result cannot be used for the assessment of the solid substance.

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:
1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Information on substance identity is not based on CAS 12042-91-0. Composition is not available. NON - Guideline study. Non- GLP. Statement from company owner is received on substance identity and composition mentioned in study report. Based on this the reliability turned into 2.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
See overall remarks
Principles of method if other than guideline:
Not relevant
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Remarks:
SPF-Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Own breed
- Weight at study initiation: 102 g (80 - 137 g)
- Fasting period before study: 16 hours
- Housing: Plastic cages filled with sawdust
- Diet (e.g. ad libitum): Altromin 1324 (of the company Altrogge in Lage/Lippe), ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: test concentrations: 25%

Doses:
6300, 8000, 10000 and 15000 mg/kg body weight
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: weighing: once a week
- Necropsy of survivors performed: yes
- Other examinations performed: body weight, macroscopic observations, section (on dead aninals)
Statistics:
LD50 values were calculated according using Probit analysis (after Linder & Weber). Confidence intervals were calculated according to Cavalli-Sforza.
Preliminary study:
Not relevant
Sex:
female
Dose descriptor:
LD50
Effect level:
9 187 mg/kg bw
95% CL:
ca. 8 383 - ca. 10 067
Mortality:
6300 mg/kg bw: 0 out of 10
8000 mg/kg bw: 2 out of 10
10000 mg/kg bw: 7 out of 10
15000 mg/kg bw: 10 out of 10
Clinical signs:
Affected animals showed difficulties with breathing and a disturbed equilibrium.
Body weight:
Animals at higher doses had lower bodyweights than animals at lower doses. it is not indicated whether this difference is significant.
Gross pathology:
Deceased animals showed reddening of the stomach and intestinal slime layer. Surviving animals did not show macroscopic abberations.
Other findings:
No data

See attached full study report for raw data.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the LD50 of Locron P towards female SPF-Wistar rats is 9187 mg/kg bw therefore it is not classified according to the criteria of the Annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS.
Executive summary:

The toxicity of Locron P towards female SPF-Wistar rats was investigated in an acute oral toxicity study comparable in methodology to OECD Guideline 401. The substance was administered to groups of ten animals at concentrations of 6300, 8000, 10000 and 15000 mg/kg bodyweight followed by a 14 -day post-dosing observation period.

Mortality was observed at 8000, 10000 and 15000 mg/kg bw: 2/10, 7/10 and 10/10, respectively. Affected animals showed difficulties with breathing and a disturbed equilibrium. Deceased animals showed reddening of the stomach and intestinal slime layer. Surviving animals did not show macroscopic abberations.

Under the test conditions, the LD50 of Locron P was found to be 9187 mg/kg bw (8383 - 10067 mg/kg bw) therefore it is not classified according to the criteria of the Annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP study according to OECD Guideline. Very concise reporting, no data on methodology, conditions, raw data not available. May become 2 when full report is available.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Guideline:
other: 84/449/EWG b.1
Guideline:
other: 83/467/EWG
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
No details reported
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
deionized
Details on oral exposure:
25% solution
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Not reported
Control animals:
not specified
Details on study design:
No details
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No lethality
Clinical signs:
Symptoms not reported
Body weight:
No details
Gross pathology:
No data
Other findings:
No data
Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the test substance Tanfix AL is not classified for acute oral toxicity according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS.
Executive summary:

In an acute oral toxicity study performed according to the OECD guideline 401, Wistar rats were given a single oral dose of test substance Tanfix AL (Aluminiumhydroxychlorid diluted at 25% in deionized water) at 2000 mg/kg bw.

No lethality and no symptoms were reported.

LD50 > 2000 mg/kg bw

Under the test conditions, the test substance is not classified for acute oral toxicity according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
9 187 mg/kg bw
Quality of whole database:
The key and the supporting studies were performed on the registered substance and are of acceptable quality (Klimisch score = 2)

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
No key study was identified.

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:
20 June 1979 - 12 July 1979
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Information on substance identity is not based on 12042-91-0. Composition is not available. NON - Guideline study. Non- GLP. Statement from company owner is received on substance identity and composition mentioned in study report. Based on this the reliability turned into 2.
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
test material certificate of analysis not included
Principles of method if other than guideline:
Not relevant
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Storage condition of test material: in the dark at 20 degrees celsius
Species:
rat
Strain:
Wistar
Remarks:
SPF-Wistar (Hoe: WISKf(SPF71))
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: HOECHST AG, Kastengrund, SPF-Zucht
- Age at study initiation: 8 - 10 weeks
- Weight at study initiation: 182 - 191 g
- Fasting period before study: Not reported
- Housing: individual Makrolon cages with wood shavings
- Diet: Rattendiät Altromin 1324 (ad libitum)
- Water: tap water, in plastic bottle (ad libitum)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 (+/- 2) °C
- Humidity (%): 50 (+/- 10) %
- Air changes (per hr): partially air-condioned rooms
- Photoperiod (hrs dark / hrs light): Not reported

IN-LIFE DATES: From: To: Not reported
Type of coverage:
occlusive
Vehicle:
water
Remarks:
deionised
Details on dermal exposure:
TEST SITE
- Area of exposure: 30 cm²
- % coverage: aluminium foil (6 x 8 cm) additional elastic plaster bandage
- Type of wrap if used: occlusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Yes. the treated skin area was rinsed with lukewarm water to remove the remaining test substance
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5 mL
- Concentration (if solution): 40% suspension
- Constant volume or concentration used: yes

VEHICLE: deionised water
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
6 female rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 21 days
- Frequency of weighing: weekly
- Necropsy of survivors performed: yes. At the end of the observation period, the surviving experimental animals were killed by CO2 gas, dissected and examined for macroscopically visible changes.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
None
Clinical signs:
No symptoms of poisoning were observed at any time during the follow-up period
Gross pathology:
The macroscopic assessment of the animals killed at the end of the observation period revealed that all animals had a lung with dark red spots (= increased blood-flow). Experience has shown that this finding is not substance-related and results from the method of asphyxiation used.

For raw data, see attached full study report

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions, the acute dermal LD50 of Locron P towards female Wistar rats is > 2000 mg/kg bw. Therefore, it is not classified according to the annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.
Executive summary:

In an acute dermal toxicity study according to methodology comparable to OECD Guideline 402, 6 female Wistar rats were exposed to Locron P at 2000 mg/kg bw during 24 hours. After the exposure period, the dressing was removed and the treated skin area was rinsed with lukewarm water to remove the remaining test substance. At the end of the observation period, the surviving experimental animals were killed by CO2 gas, dissected and examined for macroscopically visible changes.

No mortality and no clinical signs were observed during the observation period.

Dark red spots in lung (= increased blood-flow) were observed in all animals. Experience has shown that this finding is not substance-related and results from the method of asphyxiation used.

LD50 was found to be > 2000 mg/kg bw

Under the test conditions, the acute dermal LD50 of test substance Locron P is higher than 2000 mg/kg bw. Therefore, the test substance is not classified according to the annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The key study was performed on the registered substance and is of acceptable quality (Klimisch score = 2)

Additional information

Acute Toxicity: Oral route

A key study was identified (Hollander, 1975, rel.2). Toxicity of Locron P towards female SPF-Wistar rats was investigated in an acute oral toxicity study comparable in methodology to OECD Guideline 401. The substance was administered to groups of ten animals at concentrations of 6300, 8000, 10000 and 15000 mg/kg bodyweight followed by a 14 -day post-dosing observation period.

Mortality was observed at 8000, 10000 and 15000 mg/kg bw: 2/10, 7/10 and 10/10, respectively. Affected animals showed difficulties with breathing and a disturbed equilibrium. Deceased animals showed reddening of the stomach and intestinal slime layer. Surviving animals did not show macroscopic abberations.

LD50 = 9187 mg/kg bw (8383 - 10067 mg/kg bw)

An additional study performed according to the OECD guideline No 401 on the registered substance ( Hofmann, 1986, rel.2) gaves results which support those of the key study, i.e. LD50 > 2000 mg/kg bw.

Acute Toxicity: Dermal route

A key study was identified (Mayer, 1983, rel.2). In this acute dermal toxicity study according to methodology comparable to OECD Guideline 402, 6 female Wistar rats were exposed to Locron P at 2000 mg/kg bw during 24 hours. After the exposure period, the dressing was removed and the treated skin area was rinsed with lukewarm water to remove the remaining test substance. At the end of the observation period, the surviving experimental animals were killed by CO2 gas, dissected and examined for macroscopically visible changes.

No mortality and no clinical signs were observed during the observation period.

Dark red spots in lung (= increased blood-flow) were observed in all animals. Experience has shown that this finding is not substance-related and results from the method of asphyxiation used.

LD50 was found to be > 2000 mg/kg bw

Acute Toxicity: Inhalation

An acute toxicity study performed according to the OECD guideline No. 403 and in compliance with GLP, generation of the test atmosphere using the powdery test substance 202240/A as delivered by the sponsor provided a Mass Median Aerodynamic Diameter (MMAD) between 5 and 7 µm. This MMAD exceeded the required maximum diameter of 4 µm as indicated in the test guidelines.  Therefore the solid test substance was not tested. Instead a suspension in water was used to generate a test atmosphere that met the MMAD requirement. The inhalatory LC50, 4h value of an aqueous suspension of  202240/A in Wistar rats was considered to be within the range of 1 – 5 mg/L. The authors mentioned that it can not be excluded that the local toxicity contributed to the death of the animals. This is corrhoborated by the study of Driscoll (1990) where inflammation of the lung is observed following a single intratracheally instillation of substance with saline at 0.2 mg/kg or 1.0 mg/kg of Aluminium chlorohydrate impalpable.

Therefore, these results cannot be used for the assessment of the registered substance. Indeed the substance is a solid; toxicological hazard classes that apply to other physical states are not relevant and especially for local effects. As corrosivity/irritation depends on pH/concentration, the classification needs not apply if it can be shown that individual products do not meet the criteria. The absence of classification for acute inhalation for the solid substance is corroborated by the study for irritation to eyes together with the acute oral toxicity where no classification is deemed necessary according to the CLP criteria.

Justification for classification or non-classification

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self classification:

Acute toxicity (Oral):

Based on the available information, not classified according to the Regulation (EC) No. 1272/2008 and to the GHS as the LD50 is higher than 5000 mg/kg bw.

Acute toxicity (Dermal):

Based on the available information, the substance is:

- not classified according to the Annex I of the Regulation (EC) No. 1272/2008 (CLP) as the dermal LD50 is higher than 2000 mg/kg bw

- not classified according to the GHS since there is no reliable evidence that indicates the LD50 to be in the range of Category 5 values (GHS criteria not met)

Acute toxicity (Inhalation):

No relevant data available.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the Annex I of the Regulation (EC) No. 1272/2008 and to the GHS as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw≥C > 300 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to the Annex VI of the Regulation (EC) No. 1272/2008 and to the GHS are not met since narcotic effects were not observed in the acute oral toxicity studies.

Specific target organ toxicity: single exposure (Dermal):

The classification criteria according to the Annex VI of the Regulation (EC) No 1272/2008 and to the GHS as specific target organ toxicant (STOT) – single exposure, dermal are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (dermal) for a Category 1 classification (C≤ 1000 mg/kg bw) and at the guidance value (dermal) for a Category 2 classification (2000 mg/kg bw≥C > 1000 mg/kg bw). No classification is required.

The criteria for Transient Organ effects (STOT-SE Category 3) according to Annex VI of the Regulation (EC) No. 1272/2008 and to the GHS are not met since narcotic effects were not observed in the acute dermal toxicity study.

Specific target organ toxicity: single exposure (Inhalation):

No relevant data available.