Reaction mass of calcium hydrogen phosphonate and dialuminium tricalcium hexaoxide

Endpoint summary

Description of key information

There is no evidence on an intrinsic acute toxic activity of substance "reaction mass of calcium hydrogen phosphonate and dialuminium tricalcium hexaoxide" (90 % a.i.) after oral or dermal exposure. The oral and dermal LD50 rat are > 5000 mg/kg bw and > 2000 mg/kg bw, respectively. An estimate of the inhalative 4 h LC50 by route-to-route extrapolation from oral LD50 using a respiratory volume for a 250 g rat of 0.20 L/min and 100 % absorption and postulating 100 % deposition and absorption (c.f. ECHA REACH TGD R.8, Table R.8-2 and ECHA CLP TGD 3.1.3.3.4: Extrapolation oral to inhalation) results in an ATE > 26 mg/L/4h. This value is well above the cut values for classification an acute toxicity hazard of dusts.

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:

1991-02-06 to 1991-02-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP, Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

adopted February 24, 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

EEC Directive 84/449 EEC, EEC Publication No. L251, September 1984

Deviations:

no

GLP compliance:

yes

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:

TEST ANIMALS
- Source: BRL Ltd., Basel, Switzerland
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: males 186-208 g, females 152-166 g
- Fasting period before study: Feed was withheld overnight prior to dosing until approximately 3-4 hours after administration of the test substance.
- Housing: Group housing of 5 animals per sex per cage in polycarbonate cages containing purified sawdust as bedding material (Woody SPF, supplied by Broekman Institute, Someren, The Netherlands).
- Diet: standard pelleted laboratory animal diet (Kliba 343 from Klingentalmühle AG, Kaiseraugst, Switzerland) ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days before start of treatment under laboratory conditions


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C
- Humidity (%): 55 %
- Air changes (per hr): 15
- Photoperiod: Lighting was 12 hours artificial fluorescent light and 12 hours dark per day.

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

DOSE VOLUME APPLIED: 20 mL/kg body weight

Doses:

5000 mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations:
-- Mortality/Viability: At periodic intervals on the day of dosing (day 1) and twice daily thereafter for 14 days
-- Body weights: Days 1 (pre-administration), 8 and 15
-- Symptoms: At periodic intervals on the day of dosing (day 1) and once daily thereafter for 14 days. All signs of reaction to treatment were recorded with particular attention paid to changes in the skin, fur, eyes and mucous membranes, as well as to behaviour pattern, tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Remarks on result:

other: mortality: 0/10

Mortality:

No animal died during the study period.

Clinical signs:

other: No clinical signs of ill health or behavioural changes were seen during the study.

Gross pathology:

Macroscopic post mortem examination of the surviving animals at termination did not reveal any abnormalities that were considered to have arisen as an effect of treatment.

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: Regulation (EC) No 1272/2008 (EU GHS)

Conclusions:

According to CLP Regulation (EC) No 1272/2008, a classification for acute oral toxicity of substance "reaction mass of calcium hydrogen phosphonate and dialuminium tricalcium hexaoxide" is not required and labelling is not necessary.

Executive summary:

In an acute oral toxicity study according to OECD Guideline No. 401, adopted February 1987 and EEC Directive 84/449/EEC, Part B.1, September 1984, groups of fasted, approximately 8 weeks old male and female Wistar rats were given a oral single dose of substance " reaction mass of calcium hydrogen phosphonate and dialuminium tricalcium hexaoxide" (90 % a.i.) in polyethylene glycol at a dose of 5000 mg/kg bw (limit test) by gavage and observed for 14 days.

Oral LD₅₀ Males and Females > 5000 mg/kg bw.

No animal died during the study period. No clinical signs of ill health or behavioural changes were seen during the study. The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. Macroscopic post mortem examination of the surviving animals at termination did not reveal any abnormalities that were considered to have arisen as an effect of treatment.

Substance " reaction mass of calcium hydrogen phosphonate and dialuminium tricalcium hexaoxide" (90 % a.i.) is of low toxicity based on the oral LD₅₀> 5000 mg/kg bw in male and female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Quality of whole database:

Reliability 1, GLP, Guideline study

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Dose descriptor:

discriminating conc.

Value:

26 000 mg/m³ air

Quality of whole database:

Route-to-route extrapolation from oral LD50 (> 5000 mg/kg bw).

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:

1991-02-06 to 1991-02-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP, Guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

adopted February 24, 1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

EEC Directive 84/449 EEC, EEC Publication No. L251, September 1984

Deviations:

no

GLP compliance:

yes

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:

TEST ANIMALS
- Source: BRL Ltd., Basel, Switzerland
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: males 204-220 g, females 164-171 g
- Fasting period before study: no fasting period before substance application
- Housing: individually housed in polycarbonate cages containing purified sawdust as bedding material (Woody SPF, supplied by Broekman Institute, Someren, The Netherlands).
- Diet: standard pelleted laboratory animal diet (Kliba 343 from Klingentalmühle AG, Kaiseraugst, Switzerland) ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days before start of treatment under laboratory conditions


ENVIRONMENTAL CONDITIONS
- Temperature: 21°C
- Humidity: 55 %
- Air changes (per hr): 15
- Photoperiod: Lighting was 12 hours artificial fluorescent light and 12 hours dark per day.

Type of coverage:

occlusive

Vehicle:

polyethylene glycol

Details on dermal exposure:

TEST SITE
- Shaving: One day before exposure (day -1) an area of approximately 5x7 cm on the back of the animal was clipped.
- Area of exposure: approximately 25 cm³ (5x5 cm) for males and 18 cm³ (3,5x5 cm) for females
- Type of wrap if used: application on a gauze patch fixed successively to aluminium foil and flexible bandage (Coban, 3M, St. Paul, USA), with drops of petrolatum


REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test substance was removed with tissue moistened with tap-water
- Time after start of exposure: 24 hours


TEST MATERIAL
- Preparation: The formulation was prepared immediately prior to dosing. The test substance was weighed into a glass flask on an analytical balance and the vehicle (w/w) was added. Adjustment was made for specific gravity (1.126 g/mL) of vehicle. Homogeneity of the test substance in vehicle was obtained by using a magnetic stirrer, electric blender and a spatula.
- Dose level: 2000 mg/kg body weight
- Dose volume: 10 mL/kg body weight

Duration of exposure:

24 hours

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations:
-- Mortality/Viability: At periodic intervals on the day of dosing (day 1) and twice daily thereafter for 14 days
-- Body weights: Days 1 (pre-administration), 8 and 15
-- Symptoms: At periodic intervals on the day of dosing (day 1) and once daily thereafter for 14 days. All signs of reaction to treatment were recorded with particular attention paid to changes in the skin (treated skin), fur, eyes and mucous membranes, as well as to behaviour pattern, tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: mortality: 0/10

Mortality:

No animal died during the study period.

Clinical signs:

other: No clinical signs of ill health or behavioural changes were seen during the study.

Gross pathology:

Macroscopic post mortem examination of the surviving animals did not reveal any abnormalities that were considered to have arisen as an effect of treatment.

Other findings:

- Treated skin abnormalities: Erythema was observed on the treated skin area of 1 male immediately following bandage removal on day 2.

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: Regulation (EC) No 1272/2008 (EU GHS)

Conclusions:

According to CLP Regulation (EC) No 1272/2008, a classification for acute dermal toxicity of substance "reaction mass of calcium hydrogen phosphonate and dialuminium tricalcium hexaoxide" is not required and labelling is not necessary.

Executive summary:

In an acute dermal toxicity study according to OECD Guideline No. 402, adopted February 1987 and EEC Directive 84/449/EEC, Part B.3, September 1984, groups of fasted, approximately 8 weeks old male and female Wistar rats were dermally exposed to substance "reaction mass of calcium hydrogen phosphonate and dialuminium tricalcium hexaoxide" (90 % a.i.) in polyethylene glycol for 24 hours to approximately 25 cm² (males) respectively 18 cm² (females) of body surface area under occlusive conditions at a dose of 2000 mg/kg bw (limit test) and observed for 14 days.

Dermal LD₅₀ Males and Females > 2000 mg/kg bw.

No animal died during the study period. No clinical signs of ill health or behavioural changes were seen during the study. Three females showed lower body weight gain than expected for rats of this age and strain over the 2 weeks of observation.

The body weight gain shown by the males and other females over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. Erythema was observed on the skin area of 1 male immediately following bandage removal on day 2. Macroscopic post mortem examination of the surviving animals at termination did not reveal any abnormalities that were considered to have arisen as an effect of treatment.

Substance "reaction mass of calcium hydrogen phosphonate and dialuminium tricalcium hexaoxide" (90 % a.i.) is of low toxicity based on the dermal LD₅₀> 2000 mg/kg bw in male and female rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

Reliability 1, GLP, Guideline study

Additional information

Reliable, adequate and relevant acute toxicity data are available for the oral and dermal route.

All studies have been performed on rats as limit tests according to the relevant OECD Guidelines (No. 401 and 402, respectively) and EU Methods (B.1 and B.3, respectively). In none of the studies animals died, or pathological findings were seen at necropsy. The orally treated animals showed no effects on body weight gain. Three out of the five dermally treated females showed lower body weight gain than expected for rats of this age and strain over the 2 weeks of observation, whereas the body weight gain shown by the males and the other females over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. In the oral study, no clinical signs of ill health or behavioural changes were seen. Also, the dermally treated animals appeared clinically normal throughout the study, except 1 male who showed erythema on the skin area immediately following bandage removal on day 2. The oral LD₅₀ is > 5000 mg/kg bw and the dermal LD₅₀ is > 2000 mg/kg bw. Thus, there was no evidence of a relevant intrinsic toxicity of substance "reaction mass of calcium hydrogen phosphonate and dialuminium tricalcium hexaoxide" (90 % a.i.) in the oral and dermal acute toxicity tests. An estimate of the inhalative 4 h LC₅₀ by route-to-route extrapolation from oral LD₅₀ using a respiratory volume for a 250 g rat of 0.20 L/min and 100 % absorption and postulating 100 % deposition and absorption (c.f. ECHA REACH TGD R.8, Table R.8-2 and ECHA CLP TGD 3.1.3.3.4: Extrapolation oral to inhalation) results in an ATE > 26 mg/L/4h. This value is well above the cut values for classification an acute toxicity hazard of dusts. Although no substance specific intrinsic inhalative toxicity is expected, generally accepted OELs derived for inert (nuisance) dust/Particulates Not Otherwise Classified (PNOCs) of 10 mg/m³ for chronic and 20 mg/m³ for acute exposure to inhalable dust and of 1.25 mg/m³ for chronic and of 2.5 mg/m³ for acute exposure to alveolar (respirable) dust are applicable and must be adhered to, to avoid unspecific inhalative dust toxicity. At the production site, and occupational downstream users, the formation of dusts/aerosols is not significant due to specific operational conditions and implemented general dust RMMs. By adherence to the general dust limits, the risks to workers can be considered to be sufficiently controlled. Further on, in service life, the substance is embedded in polymer matrices. As there is no release from these polymer matrices during service life stages, the general population is not exposed to the substance. Thus, in accordance with REACH Regulation, Annex XI, 1. and 3., an acute toxicity study by inhalation is not justified due to toxicological as well as exposure considerations and consequently no acute inhalation test was performed.

Justification for selection of acute toxicity – oral endpoint
Only study available. Study according to OECD and EU guidelines, no deviations, GLP.

Justification for selection of acute toxicity – inhalation endpoint
Waiver in accordance with REACH Regulation, Annex XI and route-to-route extrapolation from oral LD50

Justification for selection of acute toxicity – dermal endpoint
Only study available. Study according to OECD and EU guidelines, no deviations, GLP.

Justification for classification or non-classification

There is no evidence on an intrinsic acute toxic activity of substance "reaction mass of calcium hydrogen phosphonate and dialuminium tricalcium hexaoxide” 90 % a.i. after oral or dermal exposure and through inhalation.

The LD₅₀ values for the oral and dermal routes were determined to be > 5000 mg/kg bw and > 2000 mg/kg bw, respectively. Considering the missing systemic toxicity by testing doses far above (oral route) or at (dermal route) limit dose level, no substance specific systemic acute inhalation toxicity leading to classification is expected based on route-to-route extrapolation.

In accordance with CLP Regulation (EC) No 1272/2008, substance "reaction mass of calcium hydrogen phosphonate and aluminium tricalcium hexaoxide" is not classified for acute toxicity and labelling is not required.