Reaction mass of aluminium chloride, iron dichloride, magnesium chloride and manganese dichloride

Endpoint summary

Description of key information

- oral: harmful after ingestion, according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC)

Category 4 (Warning: H302: Harmful if swallowed) according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU

- dermal: No classification due to lack of data.

- inhalation: No classification

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 935 mg/kg bw

Additional information

The test substance is a watery solution of metal chlorides and free hydrogenchloride.

The toxicity of this mixture has therefore to be regarded as a summary of the toxicity of the different ingredients. Due to the relative concentrations for acute toxicity FeCl2, MnCl2, AlCl3 and HCl are regarded. MgCl2 the only other substance of high concentration is disregarded due to the low overall toxicity of this substance and as both chloride and magnesium ions are essential for cellular life and present in every cell in high abundance.

Summary:

The summary is based on the data presented below. Calculations are based on the following composition:

	% (w/w) in solution	MW (Metal) g/mol	M = mol/L	mol % Metal		MW (compound) g/mol	% (w/w) in solution	% (w/w) dry substanz
Fe	9.5224	55.85	1.7050	62.7	FeCl2	126.75	21.60	63.18
Al	0.6813	26.98	0.2525	9.3	AlCl3	133.34	3.38	9.881
Mg	0.6497	24.30	0.2674	9.8	MgCl2	95.22	2.61	7.634
Mn	1.4832	54.94	0.2700	9.9	MnCl2	125.84	3.40	9.945
					HCl	36.46	1.3	3.80

- oral:

The ATE of the mixture is calculated based on the formula proposed in chapter 3.1.6.1 of REGULATION (EC) No 1272/2008:

100/ATE(mixture) = sum(ci/ATEi) where ci is the concentration of ingredient i in % (w/w) and ATEi is the ATE of the respective ingredient.

ATE(FeCl2) = 500 mg/kg bw, c(FeCl2) = 21.60

ATE(MnCl2) = 1300 mg/kg bw, c(MnCl2) = 3.40

ATE(AlCl3) = 578.4 mg/kg bw c(AlCl3) = 3.38

other ingredients are not relevant due to either their lack of toxicity or their low abundance.

ATE(test substance) = 1935.8

Based on this result the test substance has to be classified as harmful, Cat. 4.

- dermal:

There is no sufficient data available. As the substance is classified as corrosive, the corresponding risk management measures are deemed sufficient to cover any potential risk of dermal toxicity from the exposure to the test substance.

- inhalation:

None of the metal chlorides trigger a classification to date. Hydrochloric acid of 0.1 to 10 % (w/w) in water is only classified as metal corrosive but for acute inhalation toxicity. Accordingly the test substance should not be classified.

Detailed data per ingredient

- oral:

Toxicity of ingredients:

FeCl2:

For FeCl2 Choi 2004 A is the key study. In the toxicity test performed by OECD TG 423 (Acute Toxic Class Method) with GLP control, the LD50 value for acute oral toxicity of rats was between 300 and 2,000 mg/kg bw for ferrous chloride. Three Sprague-Dawley female rats were tested at each step and a starting dose of 300 mg/kg bw was selected. There was no mortality in the first three rats dosed with 300 mg/kg bw To confirm the starting dosage, three more rats were tested. In the second 300 mg/kg bw group, one animal was dead after one day. At the limit dosage of 2,000 mg/kg bw, all three rats died after one hour of administration. There were no effects on body weight increase in all surviving animals. The typical clinical signs of tested animals at 2,000 mg/kg bw were nasal discharge, hypoactivity, piloerection, prone position, reddish change and oedema on ears, fore-legs and hind-legs. At 300 mg/kg bw, all animals showed hypoactivity and piloerection on day 1 and some animals showed soft stool on day 2. However, these clinical signs were recovered to the normal status from day 3. The necropsy of the tested animals at 2,000 mg/kg bw showed haemorrhage on lymphatic nodes, stomach, intestine and thymus. Also, there was hypertrophy of pancreas and spleen. In one dead animal of the 300 mg/kg bw group, haemorrhage on lymphatic nodes and intestine was observed. There was no abnormality observed by microscopic examination of the surviving animals of the 300 mg/kg bw group after sacrifice on day 15.

human data:

Acute toxicity of iron ingested from normal dietary sources has not been reported. However, there are numerous reports of acute toxicity resulting from the ingestion of large overdoses of medicinal iron, especially in small children. Death has occurred from the oral ingestion of ferrous sulfate at doses ranging from 40 to 1600 mg/kg (Hoppe 1955, see chapter 7.10.3).

Acute symptoms are characterized by vomiting, diarrhoea, mild lethargy, upper abdominal pain, pallor, and hyperglycemia with more severe clinical findings including cyanosis, stupor, acidosis, haematemesis, shock, and coma (Aisen, 1990). The expert committee on vitamins and minerals considered that the following acute toxic doses apply (EVM 2003, see chapter 7.10.3):

- for infants (under the age of six years) 20 mg/kg for gastrointestinal irritation, with systemic effects not occurring below 60 mg/kg bw

- for children, 200-300 mg/kg bw

- for adults 1400 mg/kg bw.

ATE of FeCl2 = 500

MnCl2:

Due to a delay in the correspondance between the registrant of this test substance and the Manganese Consortium, no first hand animal data is available.

Secondary data from the DRAFT TOXICOLOGICAL PROFILE FOR MANGANESE, 2008, by the Agency for Toxic Substances and Disease Registry sugests, that in classical acute oral studies an LD50(rat) > 1300 mg/kg bw manganese is to be expected. Nevertheless indication is given that a single dose of 50 mg manganese chloride/kg (13.9 mg manganese/kg) already leads to intermittent neurological effects in rats.

ATE of MnCl2 = 1300

AlCl3:

For AlCl3 Stitzinger 2010 A is the key study. Female Wistar rats were treated via gavage with 2000 mg/Kg bw of the test item (35 % AlCl2OH in water) according to OECD Guideline 423 (Acute Toxic Class Method) and GLP. A LD50: > 300 — < 2000 mg/kg bw (female) based on AlCl2OH and LD50: > 900 — < 6000 mg/kg bw (female) based on the test item. All 3 animals dies at 2000 mg/kg bw (test item). In two groups tested at 300 mg/kg bw (test item) in total one animal died. 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. Clinical signs were lethargy, hunched posture, piloerection, uncoordinated movements, piloerection and/or ptosis.

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

The cut-off value for AlCl2OH is 500 mg/kg bw (= 117.02 mg/kg bw Al = 578.4 mg/kg bw AlCl3).

ATE of AlCl3 = 578.4 mg/kg bw

HCl:

No data is available. Hydrochloric acid is a strong, highly corrosive acid.In the preamble of ANNEX VII of REGULATION (EC) No 1907/2006 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL the following is stated:"In vivo testing with corrosive substances at concentration/dose levels causing corrosivity shall be avoided. Prior to testing, further guidance on testing strategies should be consulted in addition to this Annex." Therefore testing of hydrochloric acid is scientifically unjustified. The likely route of exposure is inhalation, and several studies are already provided to address the anticipated route of human exposure.

A study is therefore not required, nor considered an appropriate use of animals because of the known corrosive properties.

- dermal:

FeCl2:

For FeCl2 Choi 2004 B is the key study, a dermal limit study conducted according to OECD 402 on rats. The test substance was wetted with corn oil and applied semi-occlusively to the skin of 10 animals for a period of 24 hours. The LD50 (dermal) was greater than 2000 mg/kg bw (>881 mg Fe/kg bw). Staining of the skin was evident, with scarring observed in two animals. No deaths occurred during the study, nor were there any particular signs of toxicity except for some yellowish brown changes at the application site.

MnCl2:

No data is available.

AlCl3:

The acute dermal toxicity of Chlorhydrol ultrafine (AlCl3) towards male and female Sprague-Dawley rats was investigated in a 14 day limit test according to OECD Guideline 402 under GLP. As chloride and hydroxide are anions that are essential for cellular life and are found in living cells in high abundance their effect on toxicity is regarded negligible therefore results for this test item can be read across to aluminium trichloride (AlCl3).

Rats were exposed to a concentration of 2,000 mg/kg bw. The 14-d LD50 was found to be > 2,000 mg/kg bw. No effects on clinical signs, body weight or gross necroscopy were found.

HCl:

No data is available. Hydrochloric acid is a strong, highly corrosive acid.In the preamble of ANNEX VII of REGULATION (EC) No 1907/2006 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL the following is stated:"In vivo testing with corrosive substances at concentration/dose levels causing corrosivity shall be avoided. Prior to testing, further guidance on testing strategies should be consulted in addition to this Annex." Therefore testing of hydrochloric acid is scientifically unjustified. The likely route of exposure is inhalation, and several studies are already provided to address the anticipated route of human exposure.

A study is therefore not required, nor considered an appropriate use of animals because of the known corrosive properties.

- inhalation:

FeCl2:

No information is available on FeCl2 regarding acute inhalation toxicity. According to Annex VIII as specified under section 5.2, no testing is required via inhalatory route since high reliability studies are already in place via the oral and dermal route. Only information on FeCl3 is available. As FeCL2 is oxidised relatively fast in aerated aqueous solutions this information is of relevance and can be used for a read across. In the public IUCLID 2000 it is noted that in the rat, a single 8 hour exposure to a saturated atmosphere of aerosol generated from a 40% aqueous solution of ferric chloride led to no fatalities. The authors commented that inhalation of ferric salts as dusts and mists is irritating to the respiratory tract. However the report was not available so no further information is available from this study (BASF, 1992).

human data:

see in chapter 7.3, respiratory irritation.

MnCl2:

Due to a delay in the correspondance between the registrant of this test substance and the Manganese Consortium, no first hand animal data is available.

Secondary data from the DRAFT TOXICOLOGICAL PROFILE FOR MANGANESE, 2008, by the Agency for Toxic Substances and Disease Registry also does not deliver clear data on acute inhalation toxicity.

AlCl3:

The acute inhalation toxicity of aluminium chloride hydroxide sulfate (Al2OH2Cl2SO4) was studied in rats according to GLP and OECD 403. As chloride, hydroxide and sulfate are anions that are essential for cellular life and are found in living cells in high abundance their effect on toxicity is regarded negligible therefore results for this test item can be read across to aluminium trichloride (AlCl3). The test item 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). The mean actual dry test substance concentration was 1.6 ± 0.5 mg/L, corresponding to 6.1 ± 1.8 mg/L of the neat test substance (correction factor 3.7 for the evaporable water content). The mean nominal concentration was 9.4 mg/L resulting in a generation efficiency (ratio of mean actual concentration and nominal concentration of neat test substance) of 65%. 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 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. The inhalatory LC50, 4h value of202028/A in Wistar rats was considered to exceed 5 mg/L under the conditions of this study.

 

HCl:

Darmer 1974 is the key study for HCl. The acute inhalation toxicity of HCl was tested in rats and mice in accordance with the "Guide for Laboratory Animal Facilities and Care" (1965), prepared by the Committee on the Guide for Laboratory Animal Resources, Natl. Acad. Sci./Natl. Research Council: and Public Law 89-544, "Laboratory Animal Welfare Act," (1967).

Toxic signs in rats during exposure to HCl gas or aerosol were essentially identical. HCl was severely irritating to the eyes, mucous membranes and exposed areas of skin. The calculated LC50 values were the following:

HCl gas (5 min exposure): 40989 ppm (34803-48272)

HCl gas (30 min exposure): 4701 ppm (4129-5352)

HCl aerosol (5 min exposure): 45.6 mg/L (39.5-52.8) equivalent to 31008 ppm (26824-35845)

HCl aerosol (30 min exposure): 8.3 mg/L (7.2-9.7) equivalent to 5666 ppm (4855-6614)

Based on possible short-term effects, the SCOEL recommends a STEL (15 min) of 10 ppm (15 mg/m3). This value will be used as DNEL for acute inhalation exposure.

Information on respiratory irritation upon HCl exposure was analysed by Burleigh-Flayer 1985 in guinea pigs. Exposure of guinea pigs to hydrochloric acid aerosol by inhalation for 30 min resulted in both sensory and pulmonary irritation at all exposure concentrations, including the lowest concentration tested (320 ppm). The maximal respiratory frequency achieved during the CO2 challenge was lower in HCl-exposed animals than in controls in a concentration-dependant manner, but exposure to HCl had no apparent effect on the maximal tidal volume. Corneal opacities were noted in animals exposed to the two higher concentrations, and in a single animal exposed to 680 ppm. Tissue damage in both the airway and alveolar regions was noted both after 2 or 15 days following exposure, indicating that complete recovery was not attained in animals exposed to 1040 ppm.

human data:

see in chapter 7.3, respiratory irritation.

Justification for classification or non-classification

- oral:

Based on the assessment presented above the test substance is to be harmful after ingestion (R22 Harmful if swallowed), according to Council Directive 2001/59/EC (28th ATP of Directive 67/548/EEC) and Category 4 (Warning: H302: Harmful if swallowed) according to CLP (REGULATION (EC) No 1272/2008 OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL) as implementation of UN-GHS in the EU

- dermal:

There is no sufficient data available. As the substance is classified as corrosive, the corresponding risk management measures are deemed sufficient to cover any potential risk of dermal toxicity from the exposure to the test substance.

- inhalation:

None of the metal chlorides trigger a classification to date. Hydrochloric acid of 0.1 to 10 % (w/w) in water is only classified as metal corrosive but not for acute inhalation toxicity. Accordingly the test substance should not be classified.