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

Carcinogenicity

Description of key information

- carcinogenicity: For none of the relevant ingredients of the test substance evidence of a significant carcinogenicity potential was found. Therefore the test substance is demmed non-carcinogenic.

Justification for classification or non-classification

Based on the assessment of the carcinogenicity stated above, the test substance is deemed not to be carcinogenic and correspondingly no classification is needed.

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 carcinogenicity 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:

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
Ni	0.0080	58.69	0.0014	0.1	NiCl2	129.60	0.0176	0.0515

For none of the relevant ingredients of the test substance evidence of a significant carcinogenicity potential was found. Therefore the test substance is demmed non-carcinogenic.

 

The summary is based on the data presented below.

 

FeCl2:

There are no carcinogenicity data for iron dichloride. However, there is a reliable carcinogenicity study on the read across substance, iron trichloride, which was selected as the key study. In the repeated dose toxicity studies it has been shown that the toxicity of the different iron salts that are combined here in this category have a comparable potential of toxicity and mode of action inducing liver damage, changes in blood parameters and local irritation/corrosion in the gastro intestinal tract. Based on these similarities between the iron salts the result of the carcinogenicity study can be read-across to FeCl2.

In a good quality carcinogenicity study (Sato 1992) iron trichloride was administered to F344 rats in their drinking water for two years. Control animals received untreated drinking water. The mean body weights of the treated rats were lower than control group values for males and females. A variety of tumours developed in all groups, including the controls, but all of these neoplasms were histologically similar to those of those known to occur spontaneously in this strain of rat. There was no statistically significant increase in the incidence of any tumour found in the treated animals compared with the controls. Therefore it was concluded that iron trichloride did not exert any carcinogenic potential in F344 rats. The NOAEL was >0.5% (equivalent to 219.7 and 336 mg/kg bw/day in males and females, respectively and to 76 and 116 mgFe/kg bw/day in males and females, respectively).

human data:

Because of its potential pro-oxidant effects, there has been extensive research into possible links between iron and cancer development. These include many clinical investigations into the effects of oral (dietary) iron salts in humans and links to cancer.

The incidences of tumours in the upper digestive tract have been reported to be negatively associated with dietary iron intake (Freng 1998; Zhang 1997 see chapter 7.10.5).

Ullen et al. (1997, see chapter 7.10.3) suggested that there is a “reversed causality” in the association between dietary iron intake and cancer. In assessing reported levels of dietary and supplementary iron intake obtained through a food frequency questionnaire in a population-based, case-control study in Stockholm, these authors found that an initially-positive association between supplementary iron intake and colorectal cancer risk was reversed when intakes 5 years prior to cancer diagnosis were subtracted. These authors, thus, suggested that the initial positive association was due to the use of iron supplements to relieve early disease symptoms of iron shortage.

So although iron has been implicated in the development of cancers at various sites because of its role as a pro-oxidant, the UK Scientific Advisory Committee on Nutrition concluded that there is not enough evidence to reach conclusions for any specific links (EVM 2003, see chapter 7.10.3).

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.

In the DRAFT TOXICOLOGICAL PROFILE FOR MANGANESE, 2008, by the Agency for Toxic Substances and Disease Registry it is cocluded upon assessment of human and animal data that the potential for cancer may be low.

AlCl3:

No information is available. Based on the absence of mutagenicity, the potential of AlCl3 to act as as carcinogen is deemed very low.

HCl:

The key study for HCl is Sellakumar 1985 conducted in broad agreement with OECD 451 and is reliable with restrictions (Klimisch score 2). Daily exposure of rats to gaseous hydrochloric acid at the concentrations of 10 ppm, 6 hours a day, 5 days per week up to 128 weeks did not affect the survival or body weight of exposed animals. A higher incidence of hyperplasia of the larynx and trachea was noted at histopathology, compared to air and colony control groups. No serious irritating effects in the nasal epiththelium were obeserved. None of the treated animals developed any preneoplastic or neoplastic lesions indicating a lack of carcinogenic activity. Hydrochloric acid did not evoke a carcinogenic response in treated rats.