4-chlorophenol

Endpoint summary

Description of key information

Based on physico-chemical characteristics of the test substance, existing water solubility (relative high lipophilicity) and low molecular weight, absorption via oral and dermal route cannot be excluded. With reference to the toxicokinetic behaviour of the substance class it can be stated that also the test substance demonstrates adsorption and is presumably rapidly excreted (preferentially in the urine). Thus, no bioaccumulation potential is expected. 

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

Toxicological profile of the test substance

With regard to oral absorption, responses to the administered test substance were observed. The LD50 was determined to be 261 mg/kg bw (EHC, 1989). In a 28-d gavage study with rats, findings of toxicological relevance were observed. Tremors, tachypnea and salivation were observed from five to 30 minutes after dosing in most animals in both sexes at 500 mg/kg bw/d. A NOAEL of 100 mg/kg bw/day was deemed (Hasegawa, 2005). Furthermore, the test substance was described as corrosive to skin and mucous membranes (ECHA dissemination dossier, Joint submission, 2012).

 

Toxicokinetic assessment

No test data was available on the toxicokinetic behavior of the test substance itself. The test substance is a crystalline solid organic substance with a molecular weight of appr. 128.56 g/mol. The water solubility is reported as 26.39 g/L at 20 °C. As partition coefficient between octanol and water (log Kow) a value of appr. 2.41 is named for the test substance.

Concerning the substance class itself, two references - EHC (1989) and RIVM (1991) - serve as reliable sources to evaluate the absorption, metabolism, and excretion of chlorophenols in test animals. With reference to the toxicokinetic behaviour of the test substance it can be stated that the test substance demonstrates an adsorption and is presumably rapidly excreted (preferentially in the urine). Thus, no bioaccumulation potential is expected.

 

Absorption

Lower chlorophenols (as the test substance) are readily absorbed across the skin of both laboratory animals and humans. The results of studies on rats further suggest that absorption via the skin is greater for the sodium salts than for the parent molecules. Ingested chlorophenols are also readily taken up from the gastrointestinal tract. Data on acute toxicity clearly demonstrate that the test substance will be absorbed. For the oral route, the LD50 was determined to be 261 mg/kg bw (EHC, 1989). The absorption of inhaled lower chlorophenols by experimental animals has also been observed (RIVM, 1991).

Taken together, physico-chemical properties and experimental data indicate bioavailability of the test substance via oral, inhalation and possibly also dermal route.

 

Distribution and Metabolism

Experimental animals accumulate chlorophenols mostly in the liver and kidney, and to a lesser extent in the brain, muscle, and fat tissues (EHC, 1989). Furthermore, the highest PCP concentrations were found in the liver, kidneys and/or the intestinal tract (RIVM, 1991).

The higher levels in the liver and kidney may reflect their greater circulating blood volume, as well as the role these organs play in the detoxification and elimination of these compounds. In the animals studied, most chlorophenols were rapidly conjugated to glucuronates or sulfates in the liver. This binding, and also dechlorination and methylation, serve to detoxify these compounds (EHC, 1989).

 

Excretion

Chlorophenols are eliminated by test mammals primarily through the urine (roughly 80-90%), in both free and bound forms.Smaller amounts are eliminated in faecal matter.

A single dose of chlorophenols is virtually eliminated within one to several days. Elimination rates appear to be even more rapid for some tissues (EHC, 1989).

 

 

Read-across statement on 2-chlorophenol as surrogate substance

Furthermore, as surrogate substance liquid 2-chlorophenol (CAS No. 95-57-8) is used in several repeated dose-tests (see IUCLID Chapter 7.5, 7.7, 7.8) to evaluate the solid test substance 4-chlorophenol (CAS No. 106-48-9).

Both substances share the same molecular weight (appr. 129 g/mol). The melting point / boiling point of 2 -MCP (appr. 9 °C / appr. 175 °C) is lower compared to 4 -MCP (appr. 43 °C / appr. 220 °C). The water solubility is comparable (2-CP: 20,000 ppm, 4-CP: 27,000 ppm), as organic solvent alcohol is appropriate for 2-chlorophenol and 4-chorophenol (for more details on phys-chem data, see also ‘Toxicological profile for chlorophenols’, U.S. Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry, July 1999 [external reference]). Both substances also having comparable Koc values (2 -MCP: 2.17, 4 -MCP: 2.4). Moreover, the density of both compounds are in the same range (appr. 1.3 g/cm³). According to RIVM (1999), the toxicity of mono-chlorinated phenols, esp. on the basis of the lowest LD50 (260 – 1400 mg/kg bw), appears not to be mutually different. So, available data on oral subacute toxicitxy studies with (mono-) chlorinated phenols are regarded as reliable and appropriate for evaluation prurposes.

Thus, 2-chlorophenol is regarded as adequate surrogate substance for the test substance, 4-chlorophenol.

 

 

References

EHC 1989. Chlorophenols other than pentachlorophenol (Environmental health criteria; 93), ISBN 9241542934, World Health Organization 1989, Geneva. [http://www.inchem.org]

RIVM 1991. Integrated Criteria document Chlorophenols. Report No. 710401013, The National Institute for Public Health and the Environment (RIVM), August 1991.