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Administrative data

Link to relevant study record(s)

Description of key information

Key value for chemical safety assessment

Absorption rate - oral (%):
50
Absorption rate - dermal (%):
100
Absorption rate - inhalation (%):
100

Additional information

Toxicokinetic assessment for 1,3-cyclohexanedimethanamine

 

Introduction

 

This assessment of the absorption, distribution, metabolism and excretion of 1,3-cyclohexanedimethanamine is derived from data produced for its notification under the requirements of EC Regulation 1907/2006 and represents the Toxicokinetic assessment under Annex VIII of the Regulation.

 

Identity and physico-chemical parameters

 

  • Name – 1,3-cyclohexanedimethanamine (1,3-BAC).
  • IUPAC name – Cyclohexane-1,3-diylidimethanamine.
  • Purity – 99%.
  • Average molecular weight – 142.
  • State at 25°C – Colourless liquid.
  • Freezing point – less than -25°C.
  • Boiling temperature – 240°C.
  • Water solubility – Greater than 1000 g/L.
  • Partition coefficient – log Pow= 0.783 at 21.5°C.
  • Flash point – 116°C
  • Explosive properties – No explosive properties based on a theoretical assessment.
  • Auto-ignition temperature – 316°C.
  • Kinematic viscosity – 9.77 mm2.s-1at 20°C and 5.17 mm2.s-1at 40°C.
  • Dynamic viscosity – 9.21 mPa.s at 20°C and 4.85 mPa.s at 40°C.
  • Hydrolysis – Less than 10% hydrolysis after 5 days at 50°C.
  • Vapour pressure – 34 Pa at 25°C.
  • pH: ~11-13

 

Toxicity

 

  • Acute oral toxicity – No mortality seen at 300 mg/kg; 100% mortality seen at 2000 mg/kg. LD50estimated at 700 mg/kg. In key study, no clinical signs were seen in 300 mg/kg dose group; at 2000 mg/kg decreases in locomotor activity and irregular respiration were seen from 10 minutes after the administration. One animal was found dead within 6 hours of the administration, and two animals showed hypothermia and died the day following administration. No gross pathological findings were recorded in the 300 mg/kg group. In all animals which died, reddish change and oedema were noted in the forestomach and glandular stomach, and abnormal contents were observed in the stomach and intestine. Moreover, reddish ascites was noted in the abdominal cavity of the animal found dead on the day of administration.

  • Acute dermal toxicity – LD50calculated to be 1700 mg/kg. 2 out of four rabbits died at each of 2000 mg/kg and 1580 mg/kg dose levels, no mortality was seen at 1260 mg/kg. Bodyweights were seen to decrease in animals exposed above 1580 mg/kg. Gross pathological findings were not remarkable in the survivors necropsied 14 days after administration. Advanced autolysis prevented pathological examination in those animals found dead during the study.

  • Skin corrosivity / irritation – corrosive effects were seen in rabbits following a 3-minute dermal exposure. Necrosis of the application site was observed 1 hour after exposure.

  • Skin sensitisation – no sensitisation (0/10 animals) seen in guinea pigs.

  • Repeated dose toxicity, oral – OECD 422 Combined repeated dose toxicity with reproductive / developmental toxicity screening test (rats); NOEL = 60 mg/kg/day. One male animal died at 300 mg/kg/day, with loss of locomotor activity seen before death. Salivation was periodically observed in the 300 mg/kg/day dose group throughout the administration period. No test substance-related changes in behaviour, sensory reactivity, or motor activity were noted between the control group and treated groups throughout the study. Body weight gain was suppressed

  • Gene mutation (in-vitro) – Test substance was found to have been cytotoxic in a bacterial reverse mutation assay, however no genotoxicity / mutagenic activity was seen in four strains of Salmonella typhimurium or one strain of Escherichia coli, either with or without metabolic activation. The test substance showed the potential to induce chromosomal aberrations in Chinese Hamster Lung cells (tested in-vitro) in the absence of metabolic activation, although no chromosomal aberrations were seen under the same conditions in the presence of metabolic activation.

  • Gene mutation (in-vivo) – The test substance did not show evidence of having increased the induction of micronucleated polychromatic erythrocytes in mice in vivo.

 

Absorption

Substance has high pH and has observed corrosivity. The substance acts quickly on dermal tissue It is likely that this substance is highly absorbed no matter the exposure route. It has been shown to have significant effects on the gut and in acute studies, one animal died within 6 hours of dosing. In a repeat dose study, it was demonstrated that there was evidence of absorption.  For example, at the high dose level (300 mg/kg/day), a male died, there was suppression of bodyweight gain, and there were effects in the testes (atrophy of seminiferous tubules).  The findings in the stomach were associated with the known irritant/corrosive nature of the test material.   

 

However, local effects may be more prominent (especially since corrosion is the major mechanism of action). Systemic effects were also observed upon dermal exposure as 50% mortality was seen at the highest dose levels. 

 

Inhalation toxicity was not assessed due to the substance’s affect on dermal membranes. It can be expected that sensitive lung tissue would also experience corrosion and therefore these tests are not necessary.

 

Metabolism, Distribution and Elimination

Due to the speed at which effects have been observed in acute studies, metabolic activation is unlikely needed for substance to cause toxicity.

 

In the repeat dose study in rats, at the end of the two week recovery period, there was evidence of recovery or at least partial recovery.  This indicates that there is fairly rapid elimination of the test material and consequent amelioration of the physical (irritation/corrosive activity) and systemic toxic effects.