Registration Dossier

Administrative data

Description of key information

- Oral route: the LD50 is  > 2,000 mg/kg bw  based on a weight of evidence (OECD 423, GLP, Kr. 1 and OECD  401, GLP, Kr. 1)

- Dermal route: the LD50 of Chlorhydrol ultrafine towards male and female Sprague-Dawley rats is > 2,000 mg/kg bw (OECD , GLP, Kr. 2).

- Inhalation route: no data available on the registered substance. However, the inhalatory LC50 (rat, aerosol , 4h) value of 202028/A (CAS N°: 39290-78-3) in rats was considered to exceed 5000 mg/m3 under the conditions of this study.

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:
30 March 2010 to 22 April 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
Deviations:
no
Principles of method if other than guideline:
Not applicable.
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 11-12 weeks old) were selected.
- Weight at study initiation: 176-223 gram. Body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available.
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
- Diet (e.g. ad libitum): free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water (e.g. ad libitum): free access to tap water.
- Acclimation period: at least 5 days before start of treatment under laboratory conditions.
- Other details:
A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health.
Results of analysis for diet (nutrients and contaminants), sawdust, paper and water were assessed and did not reveal any findings that were considered to have affected the study integrity. All certificates and results of analysis are retained in the NOTOX archives.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.9 – 21.7ºC
- Humidity (%): 34 - 54% Temporary deviations from the minimum level of relative humidity of 40% occurred, but laboratory historical data do not indicate an effect of these deviations.
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day

IN LIFE DATES: From: 30 March 2010 to 22 April 2010
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Remarks:
Correction was made for the purity of the test substance, which was set at 35% for calculations in consultation with the Study Monitor.
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 4.19 mL/kg for 2000 mg/kg and 0.629 mL/kg for 300 mg/kg.

DOSAGE PREPARATION (if unusual):
The test substance was dosed undiluted as delivered by the sponsor. Dose levels were corrected for the purity of the test substance, which was set at 35% for calculations in consultation with the Study Monitor. Dose volumes were calculated as: Dose level (g/kg) / density (g/mL).

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Not indicated
Doses:
2000 mg/kg and 300 mg/kg. Single dosage, on Day 1.
Dose levels were corrected for the purity of the test substance, which was set at 35% for calculations.
No. of animals per sex per dose:
2000 mg/kg: 3 females
300 mg/kg: 6 females (2 groups of 3 animals were treated in a stepwise fashion)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days (Day 1 - Day 15)
- Frequency of observations and weighing:Clinical signs at periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15 (see 'Any other information on materials and methods inc. tables). Body weights on Days 1 (pre-administration), 8 and 15 and at death.
- Necropsy of survivors performed: yes (see 'Any other information on materials and methods inc. tables)
- Other examinations performed: Mortality/viability was observed twice daily. The time of death was recorded as precisely as possible.
Statistics:
No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).
Preliminary study:
Not applicable.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
other: Dose levels in report were corrected for the purity of the test substance, which was set at 35% for calculations
Sex:
female
Dose descriptor:
other: LD50 cut-off value
Effect level:
500 mg/kg bw
Based on:
other: Dose levels in report were corrected for the purity of the test substance, which was set at 35% for calculations
Remarks on result:
other: According to the OECD 423 test guideline
Mortality:
The incidence of mortality was as follows:
- At 2000 mg/kg: 3/3
- At 300 mg/kg: 1/3

The decedents were found dead within 24 hours post-treatment.
Clinical signs:
Clinical signs observed during the study period were as follows:
- At 2000 mg/kg: Lethargy, hunched posture, piloerection and ptosis.
- At 300 mg/kg: Lethargy, hunched posture, uncoordinated movements, piloerection and/or ptosis.

The surviving animals had fully recovered from the symptoms between Days 4 and 6.
Body weight:
The body weight gain shown by the surviving animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.
Gross pathology:
Animals that were found dead at 2000 mg/kg and 300 mg/kg showed a combination of the following findings at macroscopic post mortem examination: beginning or advanced autolysis, black-brown discolouration of the glandular mucosa of the stomach, gray-white, black-brown or reddish foci on the glandular mucosa of the stomach, hardened glandular mucosa of the stomach, dark red foci on the forestomach, distention of the stomach with gas, greenish and dark red foci on lungs, hardened lungs, dark red discolouration of the pancreas, enlargement of the spleen, reddish discolouration of the wall of the duodenum, dark red or black-brown foci on the thymus, yellowish foci on the uterus and yellowish discolouration of uterine adipose tissue in the abdominal cavity.

No macroscopic abnormalities were observed for animals at 300 mg/kg that survived until termination.

Other findings:
Not appplicable.

None

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions of this study, the oral LD50 value of 202029/A in Wistar rats was established to be within the range of 300-2000 mg/kg bw as pure equivalent. However, it was assumed that the mortality observed was due to corrosivity in the gastrointestinal tractus as this was severe local effects and not systemic effects. Therefore, the test substance is not classified for the acute oral toxicity according to the Regulation (EC) N° 1272/2008 (CLP) criteria and to the GHS.
Executive summary:

In an acute oral toxicity study performed according to OECD Guideline 423 and in compliance with GLP, the test substance (202029/A) was administered by oral gavage to three female Wistar rats at 2000 mg/kg bw. In a stepwise procedure additional groups of females were dosed at 300 mg/kg bw. Animals were then observed for mortality, clinical signs for 14 days and were all sacrificed for macroscopic examination. Dose levels were corrected for the purity of the test substance, which was set a 35% for calculation with the Study Monitor.

All animals were dead at 2000 mg/kg bw. One animal was found dead at 300 mg/kg bw. Lethargy, hunched posture, uncoordinated movements, piloerection and/or ptosis. The surviving animals had fully recovered from the symptoms between Days 4 and 6. The body weight gain shown by the surviving animals over the study period was considered to be normal.

Animals that were found dead at 2000 mg/kg bw and 300 mg/kg bw showed a combination of the following findings at macroscopic post mortem examination: beginning or advanced autolysis, black-brown discolouration of the glandular mucosa of the stomach, gray-white, black-brown or reddish foci on the glandular mucosa of the stomach, hardened glandular mucosa of the stomach, dark red foci on the forestomach, distention of the stomach with gas, greenish and dark red foci on lungs, hardened lungs, dark red discolouration of the pancreas, enlargement of the spleen, reddish discolouration of the wall of the duodenum, dark red or black-brown foci on the thymus, yellowish foci on the uterus and yellowish discolouration of uterine adipose tissue in the abdominal cavity. No macroscopic abnormalities were observed for animals at 300 mg/kg that survived until termination.

According to the protocol the animals were administered the substance as such (solution at 35%). Taking into account the substance density of 1.36 g/mL, it means that doses of 5698 mg/kg bw (4.19 mL/kg bw) and 855 mg/kg bw  (i.e 0.629 mL/kg bw) of solution at 35% were administered to the animals. However, the LD50 was expressed as equivalent pure substance and it was within the range of 300 to 2000 mg/kg bw, e.g. the pure substance was classified in cat 4. If the LD50 of the solution at 35% was considered, i.e.between 855 mg/kg bw to 5698 mg/kg bw, the lowest LD50 limit would drive to a classification acute tox. cat 4 as it ranged within 300 to 2000 mg/kg bw of acute tox. cat. 4. However, the mortality observed was due to corrosivity in the gastro-intestinal tractus, as this was severe local effects and not systemic effects. The substance was already classified in cat. 1 for the eyes (see section 7.3.1) . This could be linked to the pH value of 1 for the substance which was tested for the acute oral toxicity and the irritation to eyes.

Under the test conditions of this study, the oral LD50 value of 202029/A in Wistar rats was established to be within the range of 300-2000 mg/kg bw as pure equivalent. However, it was assumed that the mortality observed was due to corrosivity in the gastrointestinal tractus as this was severe local effects and not systemic effects. Therefore, the test substance is not classified for the acute oral toxicity according to the Regulation (EC) N° 1272/2008 (CLP) criteria 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:
Weight of evidence based on two reliable studies to fulfill the endpoint requirements.

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22 March 2010 - 05 April 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
This study has been performed according to OECD and/or EC guidelines and according to GLP principles.
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: - JMAFF, 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
Deviations:
no
Principles of method if other than guideline:
Not applicable.
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: Crl:WI(Han)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals were selected (approximately 10 weeks old).
- Weight at study initiation: body weight variation did not exceed +/- 20% of the sex mean.
- Fasting period before study: No.
- Housing:
Before exposure
Group housing of five animals per sex per cage in labelled Macrolon cages (type IV; height 18 cm) containing sterilised sawdust as bedding material (Litalabo, S.P.P.S., Argenteuil, France) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom).
After exposure
Group housing as described above, except that a paper sheet was introduced into the cage covering the bedding and cage enrichment to prevent suffocation in case of bad health condition. At the end of the Day of exposure the paper sheet was removed.
- Diet (e.g. ad libitum): Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) except during exposure to the test substance.
- Water (e.g. ad libitum): Free access to tap water except during exposure to the test substance.
- Acclimation period: At least 5 days before start of treatment under laboratory conditions.
- Health inspection: A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health

Animals 4 and 5 were replaced by spare animals, 30 minutes after start of exposure, and exposed immediately after restraining. The animals were not acclimatised for at least 15 minutes. The animals were replaced since the original animals were found dead during exposure, possibly caused by stress due to restraining. Since the exposure was ongoing, it was not possible to acclimatise the animals to restraining. It was considered that this event did not affect the exposure results for these animals.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.8 – 21.7°C
- Humidity (%): 42 - 60%
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day.

IN-LIFE DATES: From: 22 March 2010 To: 05 April 2010
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle).
Mass median aerodynamic diameter (MMAD):
>= 4 - <= 5 mm
Geometric standard deviation (GSD):
1.7
Remark on MMAD/GSD:
The Mass Median Aerodynamic Diameter (MMAD) and geometric standard deviation (gsd) were determined twice. The MMAD was 4.0 and 5.0mm and the gsd was 1.7 at both occasions.
Details on inhalation exposure:
The design of the exposure chamber is based on the flow past nose-only inhalation chamber (Am. Ind. Hyg Assoc. J. 44(12): 923-928, 1983). The chamber consisted of three animal sections with eight animal ports each. Each animal port had its own atmosphere inlet and exhaust outlet. The animals were placed in restraining tubes and connected to the animal ports. The number of animal sections and number of open inlets were adapted to the air flow in such a way that at each animal port the theoretical air flow was at least 1 L/min, which ensures an adequate oxygen supply to the animals. The main inlet of the test atmosphere was located at the top section and the main outlet was located at the bottom section. The direction of the flow of the test atmosphere guaranteed a freshly generated atmosphere for each individual animal.
The placement of the individual animals in the inhalation chamber is shown in figure 2. All components of the exposure chamber in contact with the test material were made of stainless steel, glass, rubber or plastic. To avoid exposure of the personnel and contamination of the laboratory the exposure chamber was placed in a fume hood, which maintained at a slight negative pressure.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
1.6 mg/L, corresponding to 6.1 mg/L of the neat test substance (correction factor 3.7 for the evaporable water content).
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
The test substance was administered as an aerosol by inhalation for 4 hours to one group of five male and five female Wistar rats. Animals were subjected to daily observations and determination of body weights on Days 1, 2, 4, 8 and 15. Macroscopic examination was performed after terminal sacrifice (day 15).
Statistics:
No data.
Preliminary study:
Not applicable.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occurred.
Clinical signs:
other: Clinical signs observed among most animals after exposure included lethargy, hunched posture and/or piloerection on Days 1 and/or 2. No clinical signs were observed during exposure
Body weight:
Mean body weight gain in males and females was within the range expected for rats of this strain and age used in this type of study.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
None.

None.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the inhalatory LC50, 4h value of 202028/A (aerosol) in rats was considered to exceed 5 mg/L. Therefore, no classification is required according to Regulation (EC) No 1272/2008 (CLP) and to the GHS.
Executive summary:

In an acute inhalation toxicity study performed according to OECD Guideline 403 and in compliance with GLP, groups (5/sex/dose) of Wistar rats were given 202028/Aas an aerosol by inhalation for 4 hours at 6.1 ± 1.8 mg/L of the neat test substance (correction factor 3.7 for the evaporable water content).

Animals were then observed for mortality, clinical signs and body weights for 14 days and were all sacrificed for macroscopic examination (Day 15).  

  

No mortality occurred. Clinical signs observed among most animals after exposure included lethargy, hunched posture and/or piloerection on Days 1 and/or 2. No other clinical signs were observed during exposure. The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals.

Under the test conditions of this study, the inhalatory LC50, 4h value of 202028/A (aerosol) in rats was considered to exceed 5 mg/L. Based on these results, no classification is required according to Regulation (EC) No 1272/2008 (CLP) and to the GHS.

 

Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
Common precursor(s)/breakdown product(s): Al3+ is the substance of biological interest and that the toxicological effects of Aluminium sulphate can be attributed exclusively to Al3+.

2. SOURCE AND TARGET CHEMICAL(S)
Source substance: Aluminum chloride hydroxide sulfate (CAS No 3290-78-3)
Target substance: Aluminium chloride, basic (CAS No 1327-41-9)

3. ANALOGUE APPROACH JUSTIFICATION
Based on the similar behaviour regarding toxicokinetics, data from the different soluble Aluminium salts are used in read-across approach to assess the toxicological properties of Aluminium sulphate. Hence, the data from the other soluble Aluminium salts are considered as a starting point in the hazard assessment of Aluminium sulphate taking into account the differences in bioavailability using available toxicokinetic information.

4. DATA MATRIX
See attached justification
Reason / purpose:
read-across source
Mass median aerodynamic diameter (MMAD):
>= <=
No. of animals per sex per dose:
5
Preliminary study:
Not applicable.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occurred.
Clinical signs:
other: Clinical signs observed among most animals after exposure included lethargy, hunched posture and/or piloerection on Days 1 and/or 2. No clinical signs were observed during exposure
Body weight:
Mean body weight gain in males and females was within the range expected for rats of this strain and age used in this type of study.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Other findings:
None.

None.

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the read-across approach, the inhalatory LC50, 4h value of the target substance in rats was considered to exceed 5 mg/L. Therefore, no classification is required according to Regulation (EC) No 1272/2008 (CLP) and to the GHS.
Executive summary:

In an acute inhalation toxicity study performed according to OECD Guideline 403 and in compliance with GLP, groups (5/sex/dose) of Wistar rats were given 202028/Aas an aerosol by inhalation for 4 hours at 6.1 ± 1.8 mg/L of the neat test substance (correction factor 3.7 for the evaporable water content).

Animals were then observed for mortality, clinical signs and body weights for 14 days and were all sacrificed for macroscopic examination (Day 15).  

  

No mortality occurred. Clinical signs observed among most animals after exposure included lethargy, hunched posture and/or piloerection on Days 1 and/or 2. No other clinical signs were observed during exposure. The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals.

Based on the read-across approach, the inhalatory LC50, 4h value of the target substance (aerosol) in rats was considered to exceed 5 mg/L. Based on these results, no classification is required according to Regulation (EC) No 1272/2008 (CLP) and to the GHS.

 

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
5 000 mg/m³
Quality of whole database:
Study performed on analogous was complete and sufficient to fulfill the endpoint requirements.

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:
1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Statement is provided for Identity of the test substance - no CAS number or other identification is in report. Composition has to be proved. Non GLP. OECD 402 study. Available CoA Aluminium Chlorohydrate, USP, spec No BH-0450, data May 15, 2007 wich supersedes CoA Sep 2004
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Principles of method if other than guideline:
Not applicable.
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Interfauna U.K. Limited, Wyton, Huntington
- Age at study initiation: 10 - 14 weeks
- Weight at study initiation: males: 203 - 215 g; females: 221 - 232 g
- Fasting period before study: No
- Housing: Polypropylene cages with sawdust bedding
- Diet (e.g. ad libitum): Rat and mouse expanded diet No.1, Special diet services limited, Witham, Essex, U.K., ad libitum
- Water (e.g. ad libitum): drinking water, ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 22 degrees Celsius
- Humidity (%): 45 - 60%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 13-01-1986 To: 27-01-1986
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: 5 x 12 cm on the back and flanks of the body
- % coverage: +/- 10% of the total body surface
- Type of wrap if used: bandage (surgical gauze) tightened with Elastoplast


REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: yes
- For solids, paste formed: no


VEHICLE
- No vehicle was used
Duration of exposure:
14 days
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 male and 5 female rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations: after 1 and 4 hours, daily for the remainder of the test; weighinh: weekly
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic abnormalities (section)
Statistics:
No data
Preliminary study:
No data.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality observed.
Clinical signs:
None of the animals showed any observable response during the study period.
Body weight:
No control group was used, therefore no comparison is possible
Gross pathology:
No abnormalities were noted.
Other findings:
No data

No data

Interpretation of results:
GHS criteria not met
Conclusions:
Under the test conditions of this study, the acute dermal median lethal dose to rats of Chlorhydrol ultrafine was found to be greater than 2000 mg/kg bw. Based on these results, the registered substance is not classified according to Regulation EC No.1272/2008 (CLP) and to the GHS.
Executive summary:

In an acute dermal toxicity study performed according to OECD Guideline 402 and in compliance with GLP, groups (5/sex/dose) of Sprague-Dawley rats were tested with a single dermal application of Chlorhydrol ultrafine at 2000 mg/kg bw for 24 hours. Animals were then observed for mortality, clinical signs for 14 days and were all sacrificed for macroscopic examination.

No mortality occurred. No clinical signs were observed. At necropsy, no abnormalities were noted.

The Single Dose Acute Dermal LD50 of Chlorhydrol ultrafine applied to the skin for 24 hours, is greater than 2000 mg/kg bw. Therefore the registered substance was 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:
Study complete and sufficient to fulfill the endpoint requirements.

Additional information

Acute toxicity : oral

Two studies were considered in a weight of evidence approach to assess the acute oral toxicity of the substance.

The first acute oral toxicity study (Stitzinger, 2010) was performed according to OECD Guideline 423 and in compliance with GLP. The test substance (202029/A) was administered as supplied by oral gavage to three female Wistar rats at 2000 mg/kg bw. In a stepwise procedure additional groups of females were dosed at 300 mg/kg bw. Animals were then observed for mortality, clinical signs for 14 days and were all sacrificed for macroscopic examination. Dose levels were corrected for the purity of the test substance, which was set a 35% for calculation with the Study Monitor.

All animals were dead at 2000 mg/kg bw. One animal was found dead at 300 mg/kg bw. Lethargy, hunched posture, uncoordinated movements, piloerection and/or ptosis. The body weight gain shown by the surviving animals over the study period was considered to be normal.

Under the test conditions of this study, the oral LD50 value of 202029/A in Wistar rats was established to be within the range of 300-2000 mg/kg bw as pure equivalent. However, it was assumed that the mortality observed was due to corrosivity in the gastrointestinal tractus as this was severe local effects and not systemic effects. Therefore, the test substance is not classified for the acute oral toxicity according to the Regulation (EC) N° 1272/2008 (CLP) criteria and to the GHS.

This conclusion is corrhoborated in the second acute toxicity study (Hofmann, 1988) performed according to OECD Guideline 401 and in compliance with GLP, groups (5/sex/dose) of Wistar rats were given Povimal at 2000 mg/kg bw (administered as 20% diluted in water). Animals were then observed for mortality, clinical signs for 14 days and were all sacrificed for macroscopic examination.

No mortality occurred. Both male and female rats showed retracted flanks and stayed in their respective nests. At necropsy, no effects were observed. The acute oral LD50 for was found to be greater than 2000 mg/kg bw. Based on these results, the test substance was not classified according to the Regulation (EC) N° 1272-2008 (CLP) and the GHS.

In both studies, the substance showed a pH value below 2 inducing corrosivity of the gastro-intestinal tractus leading to mortality if the substance was administered to animals as supplied (see first substance). At the contrary, no mortality was observed if the substance is diluted in water (20% concentration in vehicle) before it was administered to rats at 2000 mg/kg bw/d (see the second study). Therefore, following the weight of evidence using both studies, the substance is not classified for the acute oral toxicity according to the Regulation (EC) N° 1272-2008 (CLP) and the GHS.

Acute toxicity : dermal

A key study was identified (Jones, 1986). This acute dermal toxicity study was performed according to OECD Guideline 402 and in compliance with GLP. Groups (5/sex/dose) of Sprague-Dawley rats were tested with a single dermal application of Chlorhydrol ultrafine at 2000 mg/kg bw for 24 hours. Animals were then observed for mortality, clinical signs for 14 days and were all sacrificed for macroscopic examination. No mortality occurred. No clinical signs were observed. At necropsy, no abnormalities were noted. Under the test conditions of this study, the Single Dose Acute Dermal LD50 of Chlorhydrol ultrafine applied to the skin for 24 hours, is greater than 2000 mg/kg bw.

Acute toxicity : inhalation

No data available on the registered substance. However, one acute toxicity study performed Aluminium chloride hydroxide sulfate considered as an analogue ( CAS N°: 39290 -78 -3) was available. This study was performed according to OECD guideline 403 with Klimisch rate of 2. In this study, the inhalation LC50, 4h value (aerosol) in rats was considered to exceed 5 mg/L. Based on these results, the registered substance was considered as not harmful by inhalation route.

Justification for selection of acute toxicity – oral endpoint

OECD guideline studies performed in compliance with the GLP (Klimisch rate of 1). The results of these studies allowed to conclude on the absence of classification of the registered substance in a weight of evidence approach for the acute oral toxicity.

Justification for selection of acute toxicity – inhalation endpoint

No data available on the registered substance. However, one study performed on analogous was available.

Justification for selection of acute toxicity – dermal endpoint

Only one study performed on the registered substance was available.

Justification for classification or non-classification

Harmonized classification:

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

Self classification:

Acute toxicity via Oral route:

Based on the available data, the substance is:

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

- not classified according to the GHS as the LD50 is expected to be higher than 5000 mg/kg bw.

Acute toxicity via Dermal route:

Based on the available data, the substance is:

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

- not classified according to the GHS as the LD50 is expected to be higher than 5000 mg/kg bw.

Acute toxicity via Inhalation route:

No data available on the registered substance. However, based on the results of the study performed on analogue (CAS# 3290 -78 -3), the registered substance is not classified according to the Regulation (EC) No. 1272/2008 (CLP) and to the GHS.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the Annex VI of the Regulation (EC) No. 1272/2008 (CLP) and to the GHS as specific target organ toxicant (STOT) – single exposure, oral are not met since no systemic 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 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 (CLP) 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 studies.

Specific target organ toxicity: single exposure (Inhalation):

The classification criteria according to the Annex VI of the Regulation (EC) No 1272/2008 (CLP) and to the GHS as specific target organ toxicant (STOT) – single exposure, inhalation 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 (inhalation/dust and mists) for a Category 1 classification (C≤ 1 mg/L) and at the guidance value (inhalation/dust and mists) for a Category 2 classification (5 mg/L ≥ C > 1 mg/L). 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 inhalation toxicity study.