2-chloropropane

Endpoint summary

Additional information

IPC does not contain any functional groups that are associated with dissociation in biological fluids, indicating that dissociation of IPC within the gastrointestinal lumen or other body tissues is unlikely. The hydrolysis rate constants for IPC have been shown to not be strongly pH-dependent and are approximately doubled by the temperature increase from 27 °C to 40 °C [1]. The half-life for the hydrolysis of IPC at 40 °C was reported to be 69.9, 54.1, and 57.3 hours at pH 4.0, 7.0, and 9.0, respectively. This suggests that some hydrolysis of IPC to its corresponding alcohol may occur at the physiological pH and under the physiologically-relevant temperature of 37 °C. The low molecular weight (78.5413 g/mol), log Pow value (1.9), and physical state of IPC favour its absorption via various routes of exposure (i.e., oral, dermal, and inhalation) [2]. The high vapour pressure of IPC, however, limits its absorption following dermal exposure, and renders inhalation the most relevant route of exposure. Consistent with this prediction, pharmacokinetic analysis of IPC in rats has demonstrated that the compound is systemically absorbed following acute inhalation exposure [3]. Blood IPC concentrations were shown to increase steadily during exposure and to decrease immediately upon cessation of exposure. The authors noted that the equilibrium concentration for each dose group (3.7, 4.5, and 9.3 μg/mL in the 248, 419, and 1007 ppm dose groups, respectively) was nearly proportional to the dose, suggesting that IPC is readily cleared from the blood (and clearance is not saturated or dependent on blood flow) at the blood concentrations measured. Blood IPC concentrations were as low as 11% of peak concentrations within 48 minutes following exposure, and the plasma half-life of IPC was estimated to be 15 minutes, demonstrating that IPC is rapidly eliminated from the blood following systemic absorption. Information on the distribution, metabolism, and excretion of IPC was not available from this study. 

Dermal and oral toxicity studies on IPC in rats have shown that exposure to the compound does not result in clinical signs, mortality, or gross pathological findings, and therefore, the results of these studies do not provide any relevant information regarding the toxicokinetics of IPC from these routes of exposures [4, 5]. 

Effects related to local tissue damage were reported in 2 of the 4 available inhalation toxicity studies. In one study, in which rats were acutely exposed up to 133 g IPC/m3 of air [6], all animals died within the first hour of exposure, and hyperemic lungs were observed in all animals at necropsy. In the other study, dams were exposed to 0.61, 1.43, 2.66, or 6.67 mg IPC/L air during fetal organogenesis [7], with those in the 2 higher exposure groups showing evidence of lung damage (i.e.,dark red foci observed in 10% and 45% of the 2.66 and 6.67 mg/L groups, respectively). These findings observed in the lungs were considered not to consist of compound-related systemic effects. Additionally, no compound-related effects were reported in 2 other inhalation toxicity studies (1 acute and 1 repeated-dose study); thus, no toxicokinetic information could be derived from these studies [8, 9]. Fetal effects were also not observed in the developmental toxicity study, and thus, whether IPC crosses the placental barrier could not be inferred based on the results of this study [7]. However, considering the low log Pow (i.e.,<4) and high volatility of IPC, it is expected that excretion will occur via the lungs, and bioaccumulation is not anticipated. 

References:

[1] Schüler P, 1990, Final Report on the Investigation of Hydrolytic Degradation of 2-Chloropropane (Hydrolysis as a Function of pH) According to OECD Guideline 111, IBR Forschungs GmbH, Südkampen Nr. 31, D - 3030 Walsrode 1, Report number BAC 85-91-5051-06-89. 

[2] Lide DR, 2000,Handbook of Chemistry and Physics (81st Ed),Press Taylor & Francis Group, Boca Raton, FL, USA.

[3] Kaegler M, 1993a, Biokinetics of Inhaled Isopropyl Chloride: Acute Study on Rats, INBIFO Institut für biologische Forschung GmbH, Report number P 0542/1812.

[4] Sterner W & Chibanguza G, 1989, ISOPROPYLCHLORID Acute dermal toxicity in rats (according to OECD-guideline 402) - Limit Test -, IBR Forschungs GmbH Südkampen Nr. 31 3030 Walsrode, Report number 1-4-369-89.

[5] Chibanguza G, 1990, Acute Dermal Toxicity Test of "Isopropylchloride" in Rats, IBR Forschungs GmbH Südkampen Nr. 31 3030 Walsrode 1, Report number 10-04-0369-89.

[6] Pfenning KD, 1989, ACUTE INHALATION HAZARD TOXICITY TEST of " Isopropylchlorid" (-No. 75-29-6) (2-Chloropropone) in Wistar Rats, IBR Forschungs GmbH, Südkampen Nr. 31, D-3030 Walsrode 1, Report number 1-4-370-89.

[7] Mitterer K.E., 1992, Examination of the influence of Isopropylchloride on the Pregnant Rat and the Foetus by Inhalation, LPT Laboratory of Pharmacology and Toxicology, Redderweg 8, D-2104 Hamburg 92., Report number 6777/91.

[8] Leuschner F, 1990, ISOPROPYLCHLORID ACUTE INHALATION TOXICITY STUDY IN SPRAGUE-DAWLEY RATS (OECD-METHOD No. 403), LPT Laboratory of Pharmacology and Toxicology Redderweg 8 D-2104 Hamburg 92, Report number 5753/1/89.

[9] Kaegler M, 1993b, Inhalation Toxicity of Isopropyl Chloride: 90-Day Study on Rats, INBIFO institute für biologische Forschung, Fuggerstr. 3, 5000 Köln 90., Report number P 0542/1811.