GHS Classification Guidance for the Japanese Government

e considered to be sufficient. (Substance not classified in Category 1A) *
* This includes a case where it is described in the materials in List 2 that reproductive
toxicity is recognized with humans.
Not classified : Substance which is clearly determined to have no human
reproductive/developmental toxicity
(Decision criteria)
When it is clear from appropriate reproductive toxicity test results that a substance has
no reproductive toxicity, the substance is determined to be placed in “Not classified”. In
addition, when a substance falls under any of the following conditions, it is classified in
“Not classified”.
a) Substances are placed in “Not classified” for which adverse effects on reproductive
function, fertility, or development are reported that are considered to be induced as
non-specific secondary effects of other toxicity effects.
b) Substances are placed in "Not classified" with which the manifestation of
reproductive toxicity in animals is proved to be caused by a mechanism inherent to
the animal species or for which reproductive toxicity is not manifested in humans due
to significant differences in toxicokinetics.
c) Substances with low toxicological importance or induce only minimum effects (small
changes in sperm measurement items, incidence of spontaneous defects in fetus,
variant/ossoification retardation, fetal/pup body weight, and postnatal development
indexes) are also determined as “Not classified”.
3) Points to be noted in classification
a) When exposure of reproductive organs to test material is at a unrealistically high level
in a test using administration routes such as intravenous injection or intra-abdominal
injection, or when local damage is caused to reproductive organs by irritation or other
factors, the result of such a test is not used as the basis of classification. Adverse effects
on reproduction recognized only at an extremely high dose (for example, a dose that
induces prostration, severe inappetence, and high mortality) in an animal test are not
used as the basis of classification, unless information is available of, for example,
toxicokinetics indicating that humans are more susceptible than animals, supporting the
appropriateness of the classification.
b) A substance for which available information regarding reproductive toxicity is
determined as insufficient to make a final decision is to be placed in “Classification not
possible” because sufficient information is not available for GHS classification. An
expert's judgment shall be sought for when necessary.
166