Methylamine

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not reported, published 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented publication which meets basic scientific principles

Data source

Reference

Reference Type:

publication

Title:

Do the Hydrolysis Products, Methylamine and N,N’-Dimethylurea, Play any Role in the Methyl Isocyanate- Induced Haematological and Biochemical Changes in Rabbits?

Author:

Jeevaratnam, K., Sugendran, K., and Vaidyanathan, C.S.

Year:

1993

Bibliographic source:

Human &Experimental Toxicology, 12, 135-139

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 427 (Skin Absorption: In Vivo Method)

Deviations:

yes

Principles of method if other than guideline:

The test substance was administered subcutaneously and intravenously to the test animals.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Methylamine

EC Number:

200-820-0

EC Name:

Methylamine

Cas Number:

74-89-5

Molecular formula:

CH5N

IUPAC Name:

methanamine

Details on test material:

Methylamine (MA), 40% aqueous solution was obtained from E. Merck (India) and stored in a refrigerator because of its low boiling point.

Radiolabelling:

no

Test animals

Species:

rabbit

Strain:

other: New Zealand

Sex:

female

Details on test animals or test system and environmental conditions:

All animals were fasted over night and during the experiment, but water was allowed ad-libitum.

Administration / exposure

Type of coverage:

other: subcutaneous and intravenous

Vehicle:

water

Duration of exposure:

single injection

Doses:

2.2 mmol/kg, s.c. and (iv)

No. of animals per group:

6

Control animals:

yes

Remarks:

olive oil (injected)

Details on study design:

Blood (-0.6 ml) was drawn through a fine incision on the ear marginal vein into tubes containing heparin at 0 h (before treatment) and at 1 h, 4 h and 24 h (after treatment). Blood haemoglobin (Hb) concentration was determined by the standard cyanmethaemoglobin method and the erythrocyte volume fraction by the microhaematocrit method. Total leucocytes were counted by light microscopy using a Neubauer chamber.Total plasma protein was determined by the method of Lowry et al. and plasma albumin by the method of Doumas et al. Plasma urea was estimated by the manual diacetyl monooxime (DAM) method (cited in the original paper).

Results and discussion

Signs and symptoms of toxicity:

no effects

Remarks:

MA and DMU did not alter blood pyruvate and lactate levels. MA had no effect on the plasma urea level.

Dermal irritation:

no effects

Percutaneous absorption

Remarks on result:

other: not examined

Conversion factor human vs. animal skin:

not applicable

Any other information on results incl. tables

Of the six rabbits administered 1.0 LD 50 MIC (methyl isocyanate), two died. There were no deaths in the other groups. Rabbits administered MIC s.c. showed symptoms of respiratory distress while those animals which received either MA or DMU s.c. at equimolar concentration to MIC, appeared normal without any noticeable respiratory distress. A statistically significant increase in mean blood Hb concentration, erythrocyte volume fraction and leucocyte number was observed soon after MIC administration, the maximums being reached at 4 h while both MA and DMU administration did not affect these parameters. Plasma total protein increased significantly reaching a maximum (a 50% increase) after 4 h of MIC administration, while plasma albumin decreased with time. Both MA and DMU had no influence on either plasma total protein or plasma albumin. Furthermore, MA and DMU did not alter blood pyruvate and lactate levels. The plasma urea was significantly higher throughout the study period, reaching nearly three times the normal level 24 h after MIC administration. MA had no effect on the plasma urea level while DMU caused a marginal 20-30% increase early on and tended to return to normal by 24 h.

Applicant's summary and conclusion

Conclusions:

Methylamine (MMA) if administered subcutaneous to the rabbits did not induce haematological and biochemical changes. MMA had no influence on either plasma total protein or plasma albumin.MA did not alter blood pyruvate & lactate levels. Additionally no effects on the plasma urea level occurred.

Executive summary:

Jeevaratnam et al. administered methylamine in 1993 subcutaneous to the animals to investigate whether the observed haematological and biochemical changes observed after MIC administration to the rabbits were due only to MIC itself or if its hydrolysis metabolites play any role in these effects. Both MA and DMU administered subcutaneously in an equimolar dose to that of 1.0 LD50 MIC, 2.2 mmol/kg had no influence on these parameters, although there was a marginal increase in the plasma urea level shortly after the administration of DMU. This study establishes that the observed hematological and biochemical changes induced by MIC intoxication in rabbits are mostly due to MIC.