Registration Dossier

Administrative data

Key value for chemical safety assessment

Effects on fertility

Additional information

Studies in animals

Partly cited from SIAR for SIAM 18 (Paris, April 2004):
"No studies have been performed to explicitly address the question of reproductive effects in animals caused by 3-aminomethyl-3,5,5-trimethylcyclohexylamine. Histopathological results of a subchronic 90-day investigation on rats according to OECD TG 408 showed no effects regarding the reproductive organs (epididymides, mammary gland, ovaries, seminal vesicles, testes and uterus) in concentrations up to 160 mg/kg bw/day. Testes weights were also not affected (RCC Research and Consulting Company, 1986)."

The toxicological information regarding effects on Developmental toxicity ( no abortation or total resorption, no treatment releated effects on the pre- or post-implantation loss, no treatment releated effects on sex-ratio and on the fetal weight; CIT, 2002; see section 7.8.3 of IUCLID) and the fact that Isophorone diamine do not cause adverse effects on the examined reproductive organs in the 90 day subchronic study (RCC, 1986; see section 7.5 of IUCLID) leading to the conclusion that that effects on fertility of the substance Isophorone diamine at doses, which do not cause parental toxicity, are rather unlikely. Therefore further studies regarding effects on fertility are not necessary for Isophorone diamine.


Short description of key information:
Partly cited from SIAR for SIAM 18 (Paris, April 2004):
"No studies have been performed on the toxicity of 3-aminomethyl-3,5,5-trimethylcyclohexylamine to reproduction. Data from an oral 90-day study in rats according to OECD TG 408 did not reveal any adverse effects on the male and female reproductive organs." Together with the toxicological information of the developmental toxicity study of the substance Isophorone diamine it is concluded that that effects on fertility of the substance Isophorone diamine at doses, which do not cause parental toxicity, are rather unlikely. Therefore further studies regarding effects on fertility are not necessary for Isophorone diamine.

Effects on developmental toxicity

Description of key information
Partly cited from SIAR for SIAM 18 (Paris, April 2004):
"3-Aminomethyl-3,5,5-trimethylcyclohexylamine did not show any teratogenic or embryofetotoxic effects in a gavage study with rats performed in accordance with OECD TG 414 (2001) up to and including the highest tested dose level of 250 mg/kg bw/day."
The NOEL for maternal toxicity was 50 mg/kg bw/day, effects at 250 mg/kg bw/day were reduced food consumption and reduced body weight gain. The NOAEL for developmental toxicity is >=250 mg/kg bw/day.
Additional information

Studies in animals

Partly cited from SIAR for SIAM 18 (Paris, April 2004):

"Based on the results of a dose finding study, three groups of 24 mated female Sprague-Dawley rats

received 3-aminomethyl-3,5,5-trimethylcyclohexylamine by daily oral administration (gavage) at 0

(water = control), 10, 50 and 250 mg/kg/day from day 6 to day 19 post-coitum inclusive. On day 20

post-coitum, the dams were sacrificed and subjected to macroscopic examination. The study was

designed according to OECD TG 414.There was no treatment-related death in any of the dams.

Clinical signs were not observed, except for ptyalism in most females of the 250 mg/kg/day group

(from day 11, 12, 13 or 14 post-coitum until hysterectomy; effect not considered as adverse). Loud

breathing and hold-up in the esophagus were recorded in 4 females of this group and a significantly

lower body weight gain (-35%) was recorded after the first three days of treatment. Thereafter, the

body weights were similar to that of the controls. Over the whole treatment period, the difference

remained slight (-10 %, not statistically significant). The net body weight gain was also

significantly lower at this dose-level (-25 %) when compared to the control group. In the

250 mg/kg/day group, a significant decrease in food consumption was recorded during the treatment

period (-7%), with a more marked effect during the first three days of treatment (-21 %). Abortions

or total resorptions were not observed in any of the groups, nor were there any macroscopic

findings that were ascribed to treatment with the test item. No treatment related effects were

observed on pre- or post-implantation loss, fetal weight or sex-ratio. With respect to the fetuses, no

test item related external, soft tissue or skeletal malformations or variations were detected. There

was an increase in fetal incidence of incomplete ossification of the 5th sternebra in the 250 mg/kg

bw/day group (106/134 fetuses = 79.1 %, p < 0.01 were affected vs. 88/130 = 67.7 % in control

group, statistically insignificant on a fetus/litter basis). Because these findings are of low concern

and occur only in the presence of maternal toxicity, they are considered to be secondary. In the

same group there was a statistically nonsignificant increase in fetal incidence of incomplete

ossification of the rib(s) (9/137 fetuses = 6.7 % vs. 2/130 = 1.5 % in control group. When

ossification was incomplete, cartilage was generally present, demonstrating that the skeletal

variations recorded corresponded to slight fluctuations in the time of ossification rather than being a

persistent alteration. In conclusion, these findings were considered to be incidental and of no

toxicological significance."

The NOEL for maternotoxicity was 50 mg/kg/day and the NOAEL for embryonic development was

>250 mg/kg/day (CIT, 2002).

Justification for classification or non-classification

Because of the results of available studies the substance isophorone diamine is not classified according to 67/548/EEC and CLP regulation (1272/2008).